Search

Previous cross-sectional studies have shown that skin microbiomes in adults are distinct from those in children. However, the human skin microbiome in individuals as they sexually mature has not been studied as extensively. We performed a prospective, longitudinal study to investigate the puberty-associated shifts in skin microbiota. A total of 12 healthy children were evaluated every 6-18 months for up to 6 years. Using 16S ribosomal RNA (V1-V3) and internal transcribed spacer 1 amplicon sequencing analyzed with Divisive Amplicon Denoising Algorithm 2, we characterized the bacterial and fungal communities of five different skin and nares sites. We identified significant alterations in the composition of skin microbial communities, transitioning toward a more adult microbiome, during puberty. The microbial shifts were associated with Tanner stages (classification method for the degree of sexual maturation) and showed noticeable sex-specific differences. Over time, female children demonstrated a predominance of Cutibacterium with decreasing diversity. Among fungi, Malassezia predominated at most skin sites in more sexually mature subjects, which was more pronounced in female children. The higher relative abundances of these lipophilic taxa-C. acnes and M. restricta-were strongly associated with serum sex hormone concentrations with known influence on sebaceous gland activity. Taken together, our results support the relationship between sexual maturation, skin physiology, and the skin microbiome., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

PIWI proteins play multiple roles in germline stem cell maintenance and self-renewal. PIWI-interacting RNAs (piRNAs) associate with PIWI proteins, form effector complexes and maintain genome integrity and function in the regulation of gene expression by epigenetic modifications. Both are involved in cancer development. In this study, we investigated the expression of PIWIL-2 and piRNAs in normal human skin and epithelial tumors and its regulation during keratinocyte (KC) differentiation. Immunohistochemistry showed that PIWIL-2 was regularly expressed in the epidermis and adnexal tissue with strongest expression in sebaceous glands. Cell culture studies revealed an association of PIWIL-2 expression with the state of differentiated KC. In contrast, the PIWIL-2 expression pattern did not correlate with stem cell compartments or malignancy. piRNAs were consistently detected in KC in vitro by next-generation sequencing and the expression levels of numerous piRNAs were regulated during KC differentiation. Epidermal piRNAs were predominantly derived from processed snoRNAs (C/D-box snoRNAs), tRNAs and protein coding genes. Our data indicate that components of the PIWIL-2-piRNA pathway are present in epithelial cells of the skin and are regulated in the context of KC differentiation, suggesting a role of somatic gene regulation. However, putative roles in the maintenance of stem cell compartments or the development of malignancy in the skin were not supported by this study.

We have shown previously that endocannabinoids promote sebaceous lipogenesis, and sebocytes are involved in the metabolism of the endocannabinoid-like substance oleoylethanolamide (OEA). OEA is an endogenous activator of GPR119, a recently deorphanized receptor, which currently is being investigated as a promising antidiabetic drug target. In this study, we investigated the effects of OEA as well as the expression and role of GPR119 in human sebocytes. We found that OEA promoted differentiation of human SZ95 sebocytes (elevated lipogenesis, enhanced granulation, and the induction of early apoptotic events), and it switched the cells to a proinflammatory phenotype (increased expression and release of several proinflammatory cytokines). Moreover, we could also demonstrate that GPR119 was expressed in human sebocytes, and its small interfering RNA-mediated gene silencing suppressed OEA-induced sebaceous lipogenesis, which was mediated via c-Jun N-terminal kinase, extracellular signal-regulated kinase 1/2, protein kinase B, and CRE-binding protein activation. Finally, our pilot data demonstrated that GPR119 was downregulated in the sebaceous glands of patients with acne, arguing that GPR119 signaling may indeed be disturbed in acne. Collectively, our findings introduce the OEA/GPR119 signaling as a positive regulator of sebocyte differentiation and highlight the possibility that dysregulation of this pathway may contribute to the development of seborrhea and acne., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Current experimental research on acne pathophysiology has revealed a more complicated background than the classically reported four-factor aetiology. Cells of the pilosebaceous unit, which represent the template for the development of acne lesions, seem to be parallelly affected by endocrinological/metabolic factors as well as inflammatory/immunological ones that cooperate in sebocyte differentiation and lipogenesis. Indeed, the unique programme of sebocyte terminal differentiation and death, the so called holocrine secretion, is influenced by inflammatory and metabolic (lipid) signalling with common denominator the selective regulation of peroxisome proliferator-activated receptors. Autophagy provides substrates for energy generation and biosynthesis of new cell structure proteins contributing to the normally increased sebaceous gland metabolic functions, which are also regulated by extracellular calcium signalling, essential lipids and hormones. The ultimate differentiation product of human sebocytes, sebum, co-regulates the inflammatory sebocyte status. Sebum composition is controlled among others by Propionibacterium acnes and other bacteria, sexual hormones, neuropeptides, endogenous opioids and environmental agents, which may function as endocrine disruptors. Diet may also be an important source of substrates for the synthesis of pro-inflammatory and anti-inflammatory sebaceous lipids. Sebum changes might induce inflammation and initiate underlying immune mechanisms leading to acne lesions. Current new therapeutic efforts on acne concentrate on anti-inflammatory/immunologically active concepts, which are able to regulate sebaceous lipogenesis. At last, current molecular studies based on published molecular data sets confirmed the major role of inflammation in acne development., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Acne is a disease unique to humans and is associated with sebaceous glands that are found at high density on the scalp, forehead and face. Despite being a near universal problem in adolescence, the reason why such troublesome sebaceous glands exist at all is not well understood. Some interesting theories have been postulated including roles for skin maintenance, immunological function and perhaps even pheromones, but pre-pubertal skin which has sebaceous glands that are largely inactive, is healthy. Dystocia, obstructed labour, is unique to humans and no other animal has as much trouble giving birth. This is thought to reflect the relatively large human foetal head and proportionally small maternal pelvis. Noting the high density of sebaceous glands on the face, chest and back; these are exactly the same structures that pose the greatest obstruction during childbirth. Sebaceous glands develop after the fourth month of gestation and are large and well-developed at birth. Sebum production is also relatively high at birth. Having extra lubrication at these sites would help make the baby more slippery for birth conferring a selective advantage to successful delivery, as does the presence of the vernix caseosa, a white creamy substance, unique to humans that coats new-born infants. It is proposed that the sebaceous glands that cause acne are present on the face and forehead as they confer a selective advantage by 'lubricating' the widest parts of the new born baby to ease the passage of childbirth. Later in life, sebaceous glands may be inappropriately and pathologically primed, driven by a combination of hormones, diet and lifestyle to create acne., (Copyright © 2019 The Author. Published by Elsevier Ltd.. All rights reserved.)

Studies of senescence in the wild have traditionally focused on traits like survival or fecundity. Although efforts to measure other salient phenotypic traits and markers of relevant physiological processes are rapidly increasing, traits related to self-maintenance remain understudied in the context of aging. Uropygial or preen gland is a holocrine gland, exclusive to birds, directly linked to self-maintenance of the quality of plumage. We measured the size of uropygial glands of common gulls (Larus canus) in a cross sectional manner in order to test whether it shows the similar age-related decline as reproductive traits previously recorded in this species. Gulls with larger glands started breeding earlier in the season, indicating that gland size is a marker of individual phenotypic quality. We found a senescent decline in the onset of breeding and the size of white wing patches, a sexually dimorphic ornamental trait, while in contrast, preen gland increased with advancing age. This finding supports the view of life-history theory that in long-lived species whose lifetime reproductive success depends heavily on lifespan, self-maintenance is prioritized over reproduction. Altogether our results support the concept that senescence in the wild can be asynchronous for traits related to maintenance versus reproduction.

Full-thickness skin injury affects millions of people worldwide each year. It often leads to scar formation and loss of skin appendages even after clinical treatment. The majority of wound dressings currently used cannot achieve scarless skin regeneration with complete recovery of appendages such as hair follicles and sebaceous glands. Functional regeneration of these skin appendages is a great challenge. However, we achieved this goal by the successful development and utilization of a photo-crosslinkable sericin hydrogel (SMH) as a new type of wound dressing for repairing full-thickness skin injury. SMH implanted in a mouse full-thickness skin injury model promoted scarless wound healing with effective regeneration of hair follicles and sebaceous glands. By employing techniques of molecular biology, biochemistry, and in vivo cell tracing, we revealed the underlying repair mechanisms: SMH inhibited inflammation, stimulated angiogenesis during healing process, prevented scar tissue formation via regulating the expressions of TGF-β1 and TGF-β3, and recruited mesenchymal stem cells to injury sites for regeneration of skin appendages. Collectively, in this study, we developed a sericin-based hydrogel as a wound dressing for full-thickness skin injury repair, uncovered the functional roles of sericin hydrogels in promoting scarless skin regeneration along with effective recovery of skin appendages, and thus unveiled sericin's potential for skin wound healing.

The spiny mouse, Acomys cahirinus, shows remarkable regenerative abilities after excisional skin wounding by regrowing hair, sebaceous glands, smooth muscle, skeletal muscle and dermis without scarring. We have asked here whether this same regeneration can be seen after full thickness thermal burn injuries. Using a brass rod thermal injury model we show that in contrast to the lab mouse, Mus musculus, which forms a thick scar covered by a hairless epidermis, the spiny mouse regenerates all the tissues injured - skeletal muscle, dermis, hairs, sebaceous glands such that the skin is externally indistinguishable from its original appearance. Re-epithelialization is faster in Acomys than in Mus but ingression and proliferation of dermal fibroblasts is the same in both species. After 3 weeks the wound epithelium of Acomys has developed a covering of new hair follicles in contrast to Mus. The skeletal muscle of the panniculus carnosus in Mus shows some regeneration but it is incomplete and fibrotic whereas the Acomys muscle is replaced perfectly. There are differences in the macrophage profiles which invade the damaged tissues such as the absence of F4/80 or MOMA-2 +ve cells in Acomys which likely reflect different cytokine profiles resulting from the same injury in these two species., (Copyright © 2018 Elsevier Ltd and ISBI. All rights reserved.)

The skin surface lipids (SSL) result from the blending of sebaceous and epidermal lipids, which derive from the sebaceous gland (SG) secretion and the permeability barrier of the stratum corneum (SC), respectively. In humans, the composition of the SSL is distinctive of the anatomical distribution of the SG. Thus, the abundance of sebum biomarkers is consistent with the density of the SG. Limited evidence on the influence that the SG exerts on the SC lipidome is available. We explored the differential amounts of sebaceous and epidermal lipids in areas at different SG density with lipidomics approaches. SC was sampled with adhesive patches from forearm, chest, and forehead of 10 healthy adults (8F, 2M) after mechanical removal of sebum with absorbing paper. Lipid extracts of SC were analysed by HPLC/(-)ESI-TOF-MS. In the untargeted approach, the naïve molecular features extraction algorithm was used to extract meaningful entities. Aligned and normalized data were evaluated by univariate and multivariate statistics. Quantitative analysis of free fatty acids (FFA) and cholesterol sulfate (CHS) was performed by targeted HPLC/(-)ESI-TOF-MS, whereas cholesterol and squalene were quantified by GC-MS. Untargeted approaches demonstrated that the relative abundance of numerous lipid species was distinctive of SC depending upon the different SG density. The discriminating species included FFA, CHS, and ceramides. Targeted analyses confirmed that sebaceous FFA and epidermal FFA were increased and decreased, respectively, in areas at high SG density. CHS and squalene, which are biomarkers of epidermal and sebaceous lipid matrices, respectively, were both significantly higher in areas at elevated SG density. Overall, results indicated that the SG secretion intervenes in shaping the lipid composition of the epidermal permeability barrier.

The immunological barrier of the healthy skin is considered to be unified on the whole body surface-however, recent indirect findings have challenged this dogma since microbial and chemical milieu (e.g., sebum, sweat, and pH) exhibit remarkable differences on topographically distinct skin areas. Therefore, in the present study, we performed whole transcriptomic and subsequent pathway analyses to assess differences between sebaceous gland rich (SGR) and sebaceous gland poor (SGP) regions. Here, we provide the first evidence that different skin regions exhibit a characteristic innate and adaptive immune and barrier milieu as we could detect significantly increased chemokine (CCL2, 3, 19, 20, 23, 24) and antimicrobial peptide (S100A7, A8, A9, lipocalin, β-defensin-2) expression, altered barrier (keratin 17, 79) functions, and a non-inflammatory Th17/IL-17 dominance in SGR skin compared to SGP. Regarding pro-inflammatory molecules (IL-1α, IL-6, IL-8, IL-33, TNF-α), similarly low levels were detected in both regions. Our data may explain the characteristic topographical localization of some immune-mediated and autoimmune skin disorders and we also propose that the term "healthy skin control sample," widely used in experimental Dermatology, should only be accepted if researchers carefully specify the exact region of the healthy skin (along with the site of the diseased sample).

MC5R is one of five melanocortin receptor genes found in placental mammals. MC5R plays an important role in energy homeostasis and is also expressed in the terminal differentiation of sebaceous glands. Among placental mammals there are multiple lineages that either lack or have degenerative sebaceous glands including Cetacea (whales, dolphins, and porpoises), Hippopotamidae (hippopotamuses), Sirenia (manatees and dugongs), Proboscidea (elephants), Rhinocerotidae (rhinos), and Heterocephalus glaber (naked mole rat). Given the loss or diminution of sebaceous glands in these taxa, we procured MC5R sequences from publicly available genomes and transcriptomes, supplemented by a newly generated sequence for Choeropsis liberiensis (pygmy hippopotamus), to determine if this gene remains intact or is inactivated in association with loss/reduction of sebaceous glands. Our data set includes complete MC5R sequences for 114 placental mammal species including two individuals of Mammuthus primigenius (woolly mammoth) from Oimyakon and Wrangel Island. Complete loss or inactivation of the MC5R gene occurs in multiple placental lineages that have lost sebaceous glands (Cetacea, West Indian manatee, African elephant, white rhinoceros) or are characterized by unusual skin (pangolins, aardvarks). Both M. primigenius individuals share inactivating mutations with the African elephant even though sebaceous glands have been reported in the former. MC5R remains intact in hippopotamuses and the naked mole rat, although slightly elevated dN/dS ratios in these lineages allow for the possibility that the accumulation of inactivating mutations in MC5R may lag behind the relaxation of purifying selection. For Cetacea and Hippopotamidae, the absence of shared inactivating mutations in two different skin genes (MC5R, PSORS1C2) is consistent with the hypothesis that semi-aquatic lifestyles were acquired independently in these clades following divergence from a common ancestor., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: The main function of sebocytes is considered to be the production of lipids to moisturize the skin. However, it recently became apparent that sebocytes release chemokines and cytokines and respond to proinflammatory stimuli as well as the presence of bacteria., Objectives: To analyse the functional communication between human sebocytes and T cells., Methods: Immunofluorescence stainings for CD4 and interleukin (IL)-17 were performed on acne sections and healthy skin. Migration assays and T-cell-stimulation cultures were performed with supernatants derived from unstimulated or prestimulated SZ95 sebocytes. Dendritic cells were generated in the presence of SZ95 supernatant and subsequently used in mixed leucocyte reactions., Results: We showed that CD4 + IL-17 + T cells accumulate around the pilosebaceous unit and are in close contact with sebocytes in acne lesions. By using SZ95 sebocyte supernatant, we demonstrate a chemotactic effect of sebocytes on neutrophils, monocytes and T cells in a CXCL8-dependent manner. Furthermore, sebocyte supernatant induces the differentiation of CD4 + CD45RA + naive T cells into T helper (Th)17 cells via the secretion of IL-6, transforming growth factor-β and, most importantly, IL-1β. No direct effects of sebocytes on the function of CD4 + CD45RO + memory T cells were detected. Moreover, sebocytes functionally interact with Propionibacterium acnes in the maturation of dendritic cells, leading to antigen-presenting cells that preferentially prime Th17 cells., Conclusions: Our study provides evidence that human sebocytes actively participate in inflammatory processes in the skin by recruiting and communicating with immune cells. This interaction leads to the generation of Th17 cells, which might contribute to the pathogenesis not only of acne vulgaris, but also of several inflammatory skin diseases., (© 2017 British Association of Dermatologists.)

Background: As lipids are known to regulate macrophage functions, it is reasonable to suppose that a sebocyte-macrophage axis mediated by sebum lipids may exist., Objectives: To investigate if sebocytes could contribute to the differentiation, polarization and function of macrophages with their secreted lipids., Methods: Oil Red O lipid staining and Raman spectroscopy were used to assess the dermal lipid content and penetration. Immunohistochemistry was used to analyse the macrophage subsets. Human peripheral blood monocytes were differentiated in the presence of either supernatant from human SZ95 sebocytes or major sebum lipid components and activated with Propionibacterium acnes. Macrophage surface markers and their capacity to uptake fluorescein isothiocyanate-conjugated P. acnes were detected by fluorescence-activated cell sorting measurements. Cytokine protein levels were evaluated by enzyme-linked immunosorbent assay and Western blot analysis., Results: Sebaceous gland-rich skin had an increased dermal lipid content vs. sebaceous gland-poor skin to which all the tested sebum component lipids could contribute by penetrating the dermoepidermal barrier. Of the lipids, oleic acid and linoleic acid promoted monocyte differentiation into alternatively activated macrophages. Moreover, linoleic acid also had an anti-inflammatory effect in P. acnes-activated macrophages, inhibiting the secretion of interleukin (IL)-1β, IL-6 and tumour necrosis factor (TNF)-α. Squalene, palmitic acid, stearic acid and oleic acid augmented the secretion of IL-1β, even in the absence of P. acnes, whereas oleic acid had a selective effect of inducing IL-1β but downregulating IL-6 and TNF-α secretion., Conclusions: Our results suggest a role for sebaceous glands in modulating innate immune responses via their secreted lipids that are of possible pathological and therapeutic relevance., (© 2017 British Association of Dermatologists.)

Background: 5-Aminolevulinic acid mediated -photodynamic therapy (ALA-PDT) is known to be effective in treating acne vulgaris and other sebaceous gland-related diseases. However, the therapeutic mechanisms of ALA-PDT still remain undetermined. In this study, we aimed to investigate the effects and mechanisms of ALA-PDT on the cell growth and lipogenesis of human SZ95 sebocytes., Material and Methods: Human SZ95 sebocytes were treated with different concentration of ALA-PDT.CCK-8 assay was used to detect cell proliferation activity. Fluorescence microscope and flow cytometry were used to observe the secretion of lipids in SZ95 cells after Nile red staining. Western blotting was used to detect and analyze the protein expression level of P-p70 S6K/p70 S6K, P-4E-BP1/4E-BP1, SREBP-1, PPARγ, P-mTOR/mTOR, and P-Raptor/Raptor. Mean while, mTOR pathway activator IGF-1 and mTORC1 inhibitor rapamycin were added to observe the interferences on the ALA-PDT treatment of SZ95 cells., Results: ALA-PDT suppressed the cell growth and reduced the secretion of lipids in a dose-dependent manner in SZ95 cells. ALA-PDT reduced the protein levels of P-p70 S6K (T389), SREBP-1, PPARγ, P-mTOR and P-Raptor. IGF-1 had counter effects on ALA-PDT, and rapamycin enhanced the effects of ALA-PDT in SZ95 cells in suppressing the cell growth and reducing the secretion of lipids., Conclusion: ALA-PDT suppressed the cell growth in SZ95 cells by mTOR-p70 S6K(T389) signaling and reduced the lipogenesis in SZ95 cells by mTOR-SREBP-1/PPARγ signaling. Sebaceous glands atrophy and reduction of sebum secretion after ALA-PDT may be caused by the suppression of lipogenesis and cell growth in sebocytes., (Copyright © 2017 Elsevier B.V. All rights reserved.)

: Stem cell-based organ regeneration is purported to enable the replacement of impaired organs in the foreseeable future. Here, we demonstrated that a combination of cultured epidermal stem cells (Epi-SCs) derived from the epidermis and skin-derived precursors (SKPs) was capable of reconstituting functional hair follicles and sebaceous glands (SG). When Epi-SCs and SKPs were mixed in a hydrogel and implanted into an excisional wound in nude mice, the Epi-SCs formed de novo epidermis along with hair follicles, and SKPs contributed to dermal papilla in the neogenic hair follicles. Notably, a combination of culture-expanded Epi-SCs and SKPs derived from the adult human scalp were sufficient to generate hair follicles and hair. Bone morphogenetic protein 4, but not Wnts, sustained the expression of alkaline phosphatase in SKPs in vitro and the hair follicle-inductive property in vivo when SKPs were engrafted with neonatal epidermal cells into excisional wounds. In addition, Epi-SCs were capable of differentiating into sebocytes and formed de novo SGs, which excreted lipids as do normal SGs. Thus our results indicate that cultured Epi-SCs and SKPs are sufficient to generate de novo hair follicles and SGs, implying great potential to develop novel bioengineered skin substitutes with appendage genesis capacity., Significance: In postpartum humans, skin appendages lost in injury are not regenerated, despite the considerable achievement made in skin bioengineering. In this study, transplantation of a combination of culture-expanded epidermal stem cells and skin-derived progenitors from mice and adult humans led to de novo regeneration of functional hair follicles and sebaceous glands. The data provide transferable knowledge for the development of novel bioengineered skin substitutes with epidermal appendage regeneration capacity., (©AlphaMed Press.)

Visualizing anatomical and functional features of hair follicle development in their unperturbed environment is key in understanding complex mechanisms of hair pathophysiology and in discovery of novel therapies. Of particular interest is in vivo visualization of the intact pilosebaceous unit, vascularization of the hair bulb, and evaluation of the hair cycle, particularly in humans. Furthermore, noninvasive visualization of the sebaceous glands could offer crucial insight into the pathophysiology of follicle-related diseases and dry or seborrheic skin, in particular by combining in vivo imaging with other phenotyping, genotyping, and microbial analyses. The available imaging techniques are limited in their ability for deep tissue in vivo imaging of hair follicles and lipid-rich sebaceous glands in their entirety without biopsy. We developed a noninvasive, painless, and risk-free volumetric multispectral optoacoustic tomography method for deep tissue three-dimensional visualization of whole hair follicles and surrounding structures with high spatial resolution below 80 μm. Herein we demonstrate on-the-fly assessment of key morphometric parameters of follicles and lipid content as well as functional oxygenation parameters of the associated capillary bed. The ease of handheld operation and versatility of the newly developed approach poise it as an indispensable tool for early diagnosis of disorders of the pilosebaceous unit and surrounding structures, and for monitoring the efficacy of cosmetic and therapeutic interventions., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

The sebaceous gland displays key functions of the human skin, such as hormone synthesis in situ, antimicrobial activity and participation to inflammatory responses. Consequently, there is an emerging need of advanced in vitro models to study complex interactions between the sebaceous gland and the other skin compartments. Despite the evolution of both full-skin organ culture and reconstructed three-dimensional skin models, no satisfactory solutions have been provided for the integration of sebaceous glands and/or sebaceous gland cells in those models, probably due to their problematic maintenance both in vitro and ex vivo. We have developed a coculture model of explant skin in direct contact with immortalized SZ95 sebocytes, which resulted in overall improved structural integrity of the epidermis, higher percentage of proliferating basal epidermal cells and reduced apoptosis of differentiating keratinocytes after 6 days, as detected by Ki67 and TUNEL staining, respectively. Furthermore SZ95 sebocytes exhibited morphological and biochemical signs of normal differentiation and lipid accumulation, while interleukin-6 expression in the supernatant of the cocultures was decreased in comparison with the control. The data provide evidence of a beneficial interaction between sebocytes and skin explants and provide the rationale for their integration in future three-dimensional skin models., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background/purpose: Sebum is thought to play an important role in acne vulgaris and sebum excretion rate (SER) is often used as a marker of efficacy in acne studies. This study explored factors that could induce intra-subject variability in SER., Methods: SER was measured twice, 7 days apart, on the forehead of 40 healthy subjects. At each visit, the following parameters were also evaluated: serum androgen levels, 5-alpha-reductase type I gene expression, forehead temperature, sleep habits, diet, facial washing routine, and UV exposure., Results: There was a positive correlation between the time subjects fell asleep on Day 0 and the change in SER for the left (P = 0.010; R = 0.402) and right sides (P = 0.002; R = 0.467) of the forehead. There was a significant inverse correlation between SER and 5-alpha-reductase type 1 expression and between free testosterone levels and 5-alpha-reductase type 1 expression. In sub-analyses performed on men and women, these correlations were only significant for women., Conclusion: Variations in sleep patterns, free testosterone, and 5-alpha-reductase type 1 activity are associated with changes in sebum excretion in women. This could explain some of the inter-subject variability in SER measured between visits in clinical studies., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Impaired ectodysplasin A (EDA) receptor (EDAR) signaling affects ectodermally derived structures including teeth, hair follicles, and cutaneous glands. The X-linked hypohidrotic ectodermal dysplasia (XLHED), resulting from EDA deficiency, can be rescued with lifelong benefits in animal models by stimulation of ectodermal appendage development with EDAR agonists. Treatments initiated later in the developmental period restore progressively fewer of the affected structures. It is unknown whether EDAR stimulation in adults with XLHED might have beneficial effects. In adult Eda mutant mice treated for several weeks with agonist anti-EDAR antibodies, we find that sebaceous gland size and function can be restored to wild-type levels. This effect is maintained upon chronic treatment but reverses slowly upon cessation of treatment. Sebaceous glands in all skin regions respond to treatment, although to varying degrees, and this is accompanied in both Eda mutant and wild-type mice by sebum secretion to levels higher than those observed in untreated controls. Edar is expressed at the periphery of the glands, suggesting a direct homeostatic effect of Edar stimulation on the sebaceous gland. Sebaceous gland size and sebum production may serve as biomarkers for EDAR stimulation, and EDAR agonists may improve skin dryness and eczema frequently observed in XLHED.

Sebaceous glands perform complex functions, and they are centrally involved in the pathogenesis of acne vulgaris. Current techniques for studying sebaceous glands are mostly static in nature, whereas the gland's main function-excretion of sebum via the holocrine mechanism-can only be evaluated over time. We present a longitudinal, real-time alternative-the in vivo, label-free imaging of sebaceous glands using Coherent Anti-Stokes Raman Scattering (CARS) microscopy, which is used to selectively visualize lipids. In mouse ears, CARS microscopy revealed dynamic changes in sebaceous glands during the holocrine secretion process, as well as in response to damage to the glands caused by cooling. Detailed gland structure, plus the active migration of individual sebocytes and cohorts of sebocytes, were measured. Cooling produced characteristic changes in sebocyte structure and migration. This study demonstrates that CARS microscopy is a promising tool for studying the sebaceous gland and its associated disorders in three dimensions in vivo.

Skin stem cells resident in the bulge area of hair follicles and at the basal layer of the epidermis are multipotent and able to self-renew when transplanted into full-thickness defects in nude mice. Based on cell surface markers such as CD34 and the α6-integrin, skin stem cells can be extracted from tissue-derived cell suspensions for engraftment using the gold standard cell separation technique of fluorescence-activated cell sorting (FACS). This paper describes an alternative separation method using microfluidic devices coated with degradable antibody-functionalized hydrogels. The microfluidic method allows direct injection of tissue digestate (no preprocessing tagging of cells is needed), is fast (45 minutes from injected sample to purified cells), and scalable. This method is used in this study to isolate CD34-positive (CD34+) cells from murine skin tissue digestate, and the functional capability of these cells is demonstrated by transplantation into nude mice using protocols developed by other groups for FACS-sorted cells. Specifically, the transplantation of microfluidic isolated CD34+ cells along with dermal and epidermal cells was observed to generate significant levels of hair follicles and sebaceous glands consistent with those observed previously with FACS-sorted cells., (©AlphaMed Press.)

Background: Parasites exert important selective pressures on host life history traits. In birds, feathers are inhabited by numerous microorganisms, some of them being able to degrade feathers or lead to infections. Preening feathers with secretions of the uropygial gland has been found to act as an antimicrobial defence mechanism, expected to regulate feather microbial communities and thus limit feather abrasion and infections. Here, we used an experimental approach to test whether Great tits (Parus major) modify their investment in the uropygial gland in response to differences in environmental microorganisms., Results: We found that males, but not females, modified the size of their gland when exposed to higher bacterial densities on feathers. We also identified 16 wax esters in the uropygial gland secretions. The relative abundance of some of these esters changed in males and females, while the relative abundance of others changed only in females when exposed to greater bacterial loads on feathers., Conclusion: Birds live in a bacterial world composed of commensal and pathogenic microorganisms. This study provides the first experimental evidence for modifications of investment in the defensive trait that is the uropygial gland in response to environmental microorganisms in a wild bird.

Management of incisional scar is intimately connected to stages of wound healing. The management of an elective surgery patient begins with a thorough informed consent process in which the patient is made aware of personal and clinical circumstances that cannot be modified, such as age, ethnicity, and previous history of hypertrophic scars. In scar prevention, the single most important modifiable factor is wound tension during the proliferative and remodeling phases, and this is determined by the choice of incision design. Traditional incisions most often follow relaxed skin tension lines, but no such lines exist in high surface tension areas. If such incisions are unavoidable, the patient must be informed of this ahead of time. The management of a surgical incision does not end when the sutures are removed. Surgical scar care should be continued for one year. Patient participation is paramount in obtaining the optimal outcome. Postoperative visits should screen for signs of scar hypertrophy and has a dual purpose of continued patient education and reinforcement of proper care. Early intervention is a key to control hyperplastic response. Hypertrophic scars that do not improve by 6 months are keloids and should be managed aggressively with intralesional steroid injections and alternate modalities.

The skin and its appendages that derive from the epidermis (hair follicles, sweat glands, sebaceous glands, nails, and mammary glands) establish the integumentary system. Histologically, skin has two main layers-the epidermis and the dermis-with a subcutaneous fascia called the hypodermis, which lies deep in the dermis. The epidermis is formed of four to five layers of cells made mostly out of keratinocytes, along with three other different and less abundant cells. The dermis underlies the epidermis. The hypodermis is a looser connective tissue that is located beneath the dermis. It blends to the dermis with an unclear boundary., (© 2013 Elsevier Inc. All rights reserved.)

Lineage tracing involves labeling cells to track their subsequent behavior within the normal tissue environment. The advent of genetic lineage tracing and cell proliferation assays, together with high resolution three-dimensional (3D) imaging and quantitative methods to infer cell behavior from lineage-tracing data, has transformed our understanding of murine epidermal stem and progenitor cells. Here, we review recent insights that reveal how a progenitor cell population maintains interfollicular epidermis, whereas stem cells, quiescent under homeostatic conditions, are mobilized in response to wounding. We discuss progress in understanding how the various stem cell populations of the hair follicle sustain this complex and highly dynamic structure, and recent analysis of stem cells in sweat and sebaceous glands. The extent to which insights from mouse studies can be applied to human epidermis is also considered.

Side effects of EGFR inhibition do not include primary sebaceous gland changes. Dahlhoff et al. evaluated EGFR actions on the sebaceous glands in mutant mice with constitutively activated EGFR expression. Enlarged, hyperproliferative sebaceous glands and increased sebum levels were detected, and c-myc levels were increased. These data indicate that EGFR-induced sebocyte mechanisms are probably species-specific. The detected SCD deregulation is compatible with previous reports, whereas SCD is a marker of sebaceous differentiation, and its expression is essential for lipogenesis. As SCD expression is upregulated by TLR2 activation, there is a link between SCD overexpression and sebaceous differentiation/lipogenesis with inflammation., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

For many years, the function of the sebaceous gland (SG) was underestimated and suggested by Albert M. Kligman as a remnant of human development, a 'living fossil with a past but no future'. However, the last two decades of studies and the discovery of neuro-endocrine pathways in skin have determined the importance of the SG in cutaneous biology and homeostasis. SGs play their role in cutaneous homeostasis by contribution to local steroidogenic pathways, antimicrobial activity and display of immune (both pro- and anti-inflammatory) properties. Despite several important manuscripts and reviews regarding SG biology and function, there was an urgent need for a high-quality methodological guide through SG identification and quantitative evaluation. In this issue of Experimental Dermatology, Hinde et al. present a practical guide to SG research - outlining methods, defining immunohistochemical markers and providing guidance to both novice and more experienced SG researchers., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The skin of most mammals is characterised by the presence of sebaceous glands (SGs), whose predominant constituent cell population is sebocytes, that is, lipid-producing epithelial cells, which develop from the hair follicle. Besides holocrine sebum production (which contributes 90% of skin surface lipids), multiple additional SG functions have emerged. These range from antimicrobial peptide production and immunomodulation, via lipid and hormone synthesis/metabolism, to the provision of an epithelial progenitor cell reservoir. Therefore, in addition to its involvement in common skin diseases (e.g. acne vulgaris), the unfolding diversity of SG functions, both in skin health and disease, has raised interest in this integral component of the pilosebaceous unit. This practical guide provides an introduction to SG biology and to relevant SG histochemical and immunohistochemical techniques, with emphasis placed on in situ evaluation methods that can be easily employed. We propose a range of simple, established markers, which are particularly instructive when addressing specific SG research questions in the two most commonly investigated species in SG research, humans and mice. To facilitate the development of reproducible analysis techniques for the in situ evaluation of SGs, this methods review concludes by suggesting quantitative (immuno-)histomorphometric methods for standardised SG evaluation., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

In adult skin, self-renewing, undifferentiated hair follicle stem cells (HF-SCs) reside within a specialized niche, where they spend prolonged times as a single layer of polarized, quiescent epithelial cells. When sufficient activating signals accumulate, HF-SCs become mobilized to fuel tissue regeneration and hair growth. Here, we show that architectural organization of the HF-SC niche by transcription factor LHX2 plays a critical role in HF-SC behavior. Using genome-wide chromatin and transcriptional profiling of HF-SCs in vivo, we show that LHX2 directly transactivates genes that orchestrate cytoskeletal dynamics and adhesion. Conditional ablation of LHX2 results in gross cellular disorganization and HF-SC polarization within the niche. LHX2 loss leads to a failure to maintain HF-SC quiescence and hair anchoring, as well as progressive transformation of the niche into a sebaceous gland. These findings suggest that niche organization underlies the requirement for LHX2 in hair follicle structure and function., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objective: The importance of tear film integrity to ocular health in terrestrial mammals is well established, however, in marine mammals, the role of the tear film in protection of the ocular surface is not known. In an effort to better understand the function of tears in maintaining health of the marine mammal eye surface, we examined ocular glands of the California sea lion and began to characterize the biochemical nature of the tear film of pinnipeds., Procedures: Glands dissected from California sea lion eyelids and adnexa were examined for gross morphology, sectioned for microscopic analysis, and stained with hematoxylin and eosin. The tear film was examined using interferometry. Tears were collected from humans and pinnipeds for the analysis of protein and carbohydrate content., Results: The sea lion has sebaceous glands in the lid, but these glands are different in size and orientation compared with typical meibomian glands of terrestrial mammals. Two other accessory ocular glands located dorsotemporally and medially appeared to be identical in morphology, with tubulo-acinar morphology. An outer lipid layer on the ocular surface of the sea lion was not detected using interferometry, consistent with the absence of typical meibomian glands. Similar to human tears, the tears of pinnipeds contain several proteins but the ratio of carbohydrate to protein was greater than that in human tears., Conclusions: Our findings indicate that the ocular gland architecture and biochemical nature of the tear film of pinnipeds have evolved to adapt to the challenges of an aquatic environment., (© 2012 American College of Veterinary Ophthalmologists.)

Generation of skin appendages in engineered skin substitutes has been limited by lack of trichogenic potency in cultured postnatal cells. To investigate the feasibility and the limitation of hair regeneration, engineered skin substitutes were prepared with chimeric populations of cultured human keratinocytes from neonatal foreskins and cultured murine dermal papilla cells from adult GFP transgenic mice and grafted orthotopically to full-thickness wounds on athymic mice. Non-cultured dissociated neonatal murine-only skin cells, or cultured human-only skin keratinocytes and fibroblasts without dermal papilla cells served as positive and negative controls respectively. In this study, neonatal murine-only skin substitutes formed external hairs and sebaceous glands, chimeric skin substitutes formed pigmented hairs without sebaceous glands, and human-only skin substitutes formed no follicles or glands. Although chimeric hair cannot erupt readily, removal of upper skin layer exposed keratinized hair shafts at the skin surface. Development of incomplete pilosebaceous units in chimeric hair corresponded with upregulation of hair-related genes, LEF1 and WNT10B, and downregulation of a marker of sebaceous glands, Steroyl-CoA desaturase. Transepidermal water loss was normal in all conditions. This study demonstrated that while sebaceous glands may be involved in hair eruption, they are not required for hair development in engineered skin substitutes.

Background: MicroRNAs (miRNAs) regulate several aspects of the morphogenesis and homeostasis of the skin and its appendages, and miRNA deregulation has been shown to be associated or even causally related to several skin diseases., Objective: To evaluate the differential expression of miRNAs during sebaceous lipogenesis., Methods: Inhibition of global miRNA activity in human SZ95 sebaceous gland cells was achieved by transfection with siRNAs directed against the DICER transcript, encoding a key enzyme of miRNA biogenesis. Sebaceous lipogenesis was induced in SZ95 sebocytes by addition of linoleic acid (LA) and ciglitazone (CIG) and microarray-based miRNA expression profiles were obtained on an Agilent platform. The expression of selected miRNA candidates was measured by Taqman quantitative real-time RT-PCR. Increased activity of one validated miRNA was attained by transfecting SZ95 sebocytes with miR-574-3p mimics., Results: Downregulation of sebaceous lipogenesis was detected in DICER-impaired SZ95 sebocytes. Using microarrays, we identified twelve significantly upregulated and nine significantly downregulated miRNAs in LA- and CIG-treated SZ95 sebocytes as compared to non-treated cells. Validation of a subset of miRNA candidates by qRT-PCR confirmed upregulation of mIR-203 and miR-574-3p and downregulation of miR-7 during sebaceous lipogenesis. The two upregulated miRNAs have been previously implied in keratinocyte differentiation. Increased activity of miR-574-3p augmented lipogenesis in SZ95 sebocytes., Conclusion: Global miRNA activity is essential for lipid synthesis in human SZ95 sebocytes. Individual miRNAs are likely to play a significant role during sebaceous lipogenesis., (Copyright © 2013 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.)

The preen gland is a holocrine sebaceous gland of the avian integument which produces an oily secretion that is spread on the plumage during preening. It has been suggested that birds may defend themselves against feather-degrading bacteria (FDB) and other potential pathogens using preen gland secretions. However, besides some in vitro studies, the in vivo bacterial inhibitory effects of the preen oil on the abundance of feather-associated bacterial species has not yet been studied in passerines. Here we tested the effect of gland removal on the abundance of FDB and other-cultivable bacterial loads (OCB) of male house sparrows (Passer domesticus). Our results did not support earlier results on in vitro antibacterial activity of preen oil against FDB since the absence of the preen gland did not significantly affect their loads related to the control birds. In contrast, we found that preen gland removal led to higher loads of OCB. This result suggests that the antimicrobial spectrum of the preen oil is broader than previously thought and that, by reducing the overall feather bacterial loads, the preen gland could help birds to protect themselves against a variety of potentially harmful bacteria.

The changes of the sebaceous gland number, size and sebocyte proliferative activity were studied in the temporal area of the scalp skin in the male individuals aged 10 to 70 years (n=77, autopsy material). The minimal number of the sebaceous glands was observed in children. This index rapidly increased thereafter, reaching a peak at 20 years, then gradually decreased. These parameters correlated with the sebaceous gland size, sebocyte proliferative activity and total blood testosterone level. In older men the size of the sebaceous glands was increased.

Three-dimensional ultrasound microscopy with the central frequency of 120 MHz made it possible to observe in vivo sebaceous glands at the deep part of the dermis at microscopic level. The deformation displacements were measured by an established testing device, and the viscoelasticity was estimated from the measured displacements and Voigt model. The occupancy, density or average size of sebaceous glands was compared with the viscoleasticity. There were three major findings in the comparisons. First, the occupancy of sebaceous gland showed negative correlation with the elasticity. Second, the density of sebaceous glands showed positive correlation with the viscosity. Third, the average size of sebaceous glands showed negative correlation with the viscosity. In conclusion, viscoelastic property of human skin is strongly influenced by the morphology of the sebaceous glands.

Activation of epithelial stem cells and efficient recruitment of their proliferating progeny plays a critical role in cutaneous wound healing. The reepithelialized wound epidermis has a mosaic composition consisting of progeny that can be traced back both to epidermal and several types of hair follicle stem cells. The contribution of hair follicle stem cells to wound epidermis is particularly intriguing as it involves lineage identity change from follicular to epidermal. Studies from our laboratory show that hair follicle-fated bulge stem cells commit only transient amplifying epidermal progeny that participate in the initial wound re-epithelialization, but eventually are outcompeted by other epidermal clones and largely disappear after a few months. Conversely, recently described stem cell populations residing in the isthmus portion of hair follicle contribute long-lasting progeny toward wound epidermis and, arguably, give rise to new interfollicular epidermal stem cells. The role of epithelial stem cells during wound healing is not limited to regenerating stratified epidermis. By studying regenerative response in large cutaneous wounds, our laboratory uncovered that epithelial cells in the center of the wound can acquire greater morphogenetic plasticity and, together with the underlying wound dermis, can engage in an embryonic-like process of hair follicle neogenesis. Future studies should uncover the cellular and signaling basis of this remarkable adult wound regeneration phenomenon., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Evolutionary modification has produced a spectrum of animal defence traits to escape predation, including the ability to autotomize body parts to elude capture. After autotomy, the missing part is either replaced through regeneration (for example, in urodeles, lizards, arthropods and crustaceans) or permanently lost (such as in mammals). Although most autotomy involves the loss of appendages (legs, chelipeds, antennae or tails, for example), skin autotomy can occur in certain taxa of scincid and gekkonid lizards. Here we report the first demonstration of skin autotomy in Mammalia (African spiny mice, Acomys). Mechanical testing showed a propensity for skin to tear under very low tension and the absence of a fracture plane. After skin loss, rapid wound contraction was followed by hair follicle regeneration in dorsal skin wounds. Notably, we found that regenerative capacity in Acomys was extended to ear holes, where the mice exhibited complete regeneration of hair follicles, sebaceous glands, dermis and cartilage. Salamanders capable of limb regeneration form a blastema (a mass of lineage-restricted progenitor cells) after limb loss, and our findings suggest that ear tissue regeneration in Acomys may proceed through the assembly of a similar structure. This study underscores the importance of investigating regenerative phenomena outside of conventional model organisms, and suggests that mammals may retain a higher capacity for regeneration than was previously believed. As re-emergent interest in regenerative medicine seeks to isolate molecular pathways controlling tissue regeneration in mammals, Acomys may prove useful in identifying mechanisms to promote regeneration in lieu of fibrosis and scarring.

Oily skin (seborrhea) is a common cosmetic problem that occurs when oversized sebaceous glands produce excessive amounts of sebum giving the appearance of shiny and greasy skin. This paper overviews the main concepts of sebaceous gland anatomy and physiology, including the biosynthesis, storage and release of sebum, as well as its relationship to skin hydration and water barrier function. We also address how skin oiliness may vary according to diet, age, gender, ethnicity and hot humid climates. The deeper understanding of this skin type provides the opportunity to better guide patients regarding skin care and also assist in the development of sebosuppressive agents., (Copyright © 2012 S. Karger AG, Basel.)

Sebaceous glands secrete sebum onto the skin surface in a holocrine manner and as such a thin lipid layer is formed as a physiological barrier. In the present study, extracellular level of triacylglycerols (TG), a major sebum component, as well as intracellular TG accumulation was augmented in insulin-differentiated hamster sebocytes (DHS). The DHS exhibited phosphatidylserine exposure in an apoptosis-independent manner. In addition, intracellular ATP level and membrane-transporter activity using a substrate, Rhodamine 123, were highly detectable in the DHS rather than in the undifferentiated hamster sebocytes. A membrane-transporter activating reagent, 2'(3')-O-(4-benzoylbenzoyl) adenosine 5'-triphosphate (BzATP), enhanced transporter activity, extracellular TG level, and phosphatidylserine exposure in the DHS. Both transporter activity and TG secretion were suppressed by R-verapamil, a potent membrane-transporter inhibitor, in the BzATP-treated and untreated DHS. Furthermore, the gene expression and production of ATP-binding cassette subfamily B member 1 (ABCB1) were augmented in the DHS. ABCB1 was also detectable in sebaceous glands in the skin of hamsters. Moreover, the cell-differentiation- and BzATP-augmented transporter activity and TG secretion were dose-dependently inhibited by adding not only an ABCB1 antibody but also a selective inhibitor of ABCB1, PSC833. Thus, these results provide novel evidence that ABCB1 is involved in sebum secretion in the DHS, which is associated with non-apoptotic phosphatidylserine exposure and the increased level of intracellular ATP. These findings should accelerate the understanding of sebum secretion occurring in a holocrine-independent manner in sebaceous glands, and may contribute to the development of therapies for sebaceous gland disorders such as acne, seborrhea, and xerosis., (Copyright © 2011 Elsevier B.V. All rights reserved.)

The pilosebaceous unit of the human skin consists of the hair follicle and the sebaceous gland. Within this "mini-organ", the sebaceous gland has been neglected by the researchers of the field for several decades. Actually, it was labeled as a reminiscence of human development ("a living fossil with a past but no future"), and was thought to solely act as a producer of sebum, a lipid-enriched oily substance which protects our skin (and hence the body) against various insults. However, due to emerging research activities of the past two decades, it has now become evident that the sebaceous gland is not only a "passive" cutaneous "relic" to establish the physico-chemical barrier function of the skin against constant environmental challenges, but it rather functions as an "active" neuro-immuno-endocrine cutaneous organ. This review summarizes recent findings of sebaceous gland research by mainly focusing on newly discovered physiological functions, novel regulatory mechanisms, key events in the pathology of the gland, and future directions in both experimental and clinical dermatology.

Recent breakthroughs in the generation of induced pluripotent stem cells (iPSCs) have provided a novel renewable source of cells with embryonic stem cell-like properties, which may potentially be used for gene therapy and tissue engineering. Although iPSCs have been differentiated into various cell types, iPSC-derived keratinocytes have not yet been obtained. In this study, we report the in vitro differentiation of mouse iPSCs into a keratinocyte lineage through sequential applications of retinoic acid and bone-morphogenetic protein-4 and growth on collagen IV-coated plates. We show that iPSCs can be differentiated into functional keratinocytes capable of regenerating a fully differentiated epidermis, hair follicles, and sebaceous glands in an in vivo environment. Keratinocytes derived from iPSCs displayed characteristics similar to those of primary keratinocytes with respect to gene and protein expression, as well as their ability to differentiate in vitro and to reconstitute normal skin and its appendages in an in vivo assay. At present, no effective therapeutic treatments are available for many genetic skin diseases. The development of methods for the efficient differentiation of iPSCs into a keratinocyte lineage will enable us to determine whether genetically corrected autologous iPSCs can be used to generate a permanent corrective therapy for these diseases.

The variation in hair coat and skin histology traits of Criollo Limonero cattle was analyzed using 213 Criollo Limonero females. Skin biopsies were obtained from slick-haired (N=16) and normal-haired (N=14) animals. Measured traits included hair length (HL), color coat (CC), number of hair follicles per square centimeter (NHF), sweat glands per square centimeter (NSG), sweat glands size (SGS), sebaceous glands per square centimeter (NSBG), blood vessels per square centimeter (NBV), and thickness of epidermis (TE). Hair length differed (P<0.001) between slick- and normal-haired animals (4.9 ± 0.12 vs 10.9 ± 0.20, respectively). Differences (P<0.01) in CC (Bayo = 144/67.6% vs Red = 69/32.4%) and HL (slick-haired = 199/93.4% vs normal-haired = 14/6.5%) were found. Distribution of slick- and normal-haired animals differed (P<0.01) between bayo-coated and red-coated (139/62.2% vs 9/4.2%; respectively). Most (P<0.05) red-coated animals belonged to a single family. No differences (P>0.05) were found between slick-haired and normal-haired animals in NHF (637 ± 164 vs 587 ± 144, respectively), NSG (556 ± 134 vs 481 ± 118, respectively), NSBG (408 ± 87 vs 366 ± 77, respectively), NBV (1628 ± 393 vs 1541 ± 346, respectively), and TE (1.24 ± 0.14 vs 1.32 ± 0.12, respectively). However, SGS was greater (P<0.01) in slick-haired than normal-haired animals. In conclusion, Criollo Limonero cattle are predominantly bayo-coated, slick-haired, with a reduced number of hair follicles relative to Zebu cattle, sweat and sebaceous glands in proportion to hair follicle numbers, and with a high blood flow irrigating the skin. There is a sub-group of red-coated animals with yellow or cream skin, thicker epidermis, and with a higher frequency of normal-haired animals. It appears that the slick hair gene has been favored by natural selection in this breed.

Melanocortins have been implicated in human sebum secretion for a long time. However, the signalling pathways of α-melanocyte-stimulating hormone (α-MSH) in human sebocytes expressing melanocortin receptors (MC-Rs) are still poorly understood. Because calcium ions play a central role in MC-R signalling, we investigated whether α-MSH affects calcium signalling in the immortalized human sebocyte cell line SZ95. In addition, we investigated the impact of α-MSH on MC-1R expression and lipid synthesis in these cells. α-MSH increased intracellular calcium levels. α-MSH-mediated calcium mobilization originated from intracellular calcium stores and was mediated by inositol triphosphate. Moreover, α-MSH increased MC-1R immunoreactivity and lipid synthesis in SZ95 sebocytes in the presence of testosterone. Our data demonstrate that α-MSH in human sebocytes controls a key cellular signalling pathway, the calcium ion response, which may coordinate MC-1R-mediated sebum secretion., (© 2010 John Wiley & Sons A/S.)

Background: The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor. When environmental pollutants, including chemical carcinogens, bind to AhR, the receptor translocates to nucleus and transcriptionally activates target genes including drug metabolizing enzymes such as P450s. Recent studies have shown that AhR mediates various responses, including cellular growth, differentiation, immune system and development., Objective: In this study, we investigated the physiological function of AhR in skin., Methods: Distribution of AhR in murine skin was examined by immunohistochemistry. Expression of a target gene which is transcriptionally activated by AhR is analysed by RT-PCR., Results: We found that AhR co-localizes with the transcriptional repressor B lymphocyte maturation protein 1 (Blimp1) in sebaceous gland. In this report, we show that expression of Blimp1 is induced by treatment with AhR ligands, such as methylcolanthrene (MC) in sebocyte and keratinocyte cell lines. Exposure to ultraviolet B, which has been reported to generate AhR ligand intracellularly, also increased Blimp1 mRNA. This ligand-dependent induction of Blimp1 requires the expression of both AhR and ARNT, since transfection of siRNA specific to either AhR or ARNT significantly reduced Blimp1 mRNA in response to MC. Analysis using kinase inhibitors revealed that ligand-dependent induction of Blimp1, but not that of CYP1A1, is inhibited by staurosporine. TPA, a potent activator of protein kinase C, increased Blimp1 mRNA but not CYP1A1., Conclusion: These data indicate that Blimp1 is a novel AhR-target gene in epidermal keratinocyte and sebocyte., (Copyright 2010 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.)

Preen glands exist in almost every bird species and several non-exclusive functions have been proposed for this gland and the oils that it produces. One function generally admitted is that the oily secretions of the preen gland would provide a waterproofing layer when spread over feathers. Alternatively, several authors have proposed that plumage waterproofness is mostly due to the spatial micro-structure of feathers. The purpose of this study was to examine, by manipulating the access to the preen gland, the effect of the preen oil on the plumage waterproofness and condition. To explore this question, we carried out two independent experiments where we temporarily blocked access to the preen gland secretions with a removable mechanism in one group of captive mallards (Anas platyrhynchos), whilst a second group of birds had access to gland secretions. In a long-term experiment (3 months of treatment) and a short-term experiment (10 days), we measured plumage water retention and condition. After 3 months without access to preen glands, we found a significant decrease of plumage condition and an associated increase in plumage water retention. Moreover, we found a significant correlation between plumage condition and water retention ability. In contrast, after 10 days of treatment, no significant effect was found on plumage condition and water retention. Our study shows that preen oil acts to maintain plumage condition and suggests that feather microstructure is essential to maintain plumage waterproofness.

The demographic profile of facial acne vulgaris has changed during the past several decades; 12 years of age is no longer the low end of the "normal" range for onset of acne. The available epidemiologic evidence raises more questions than it answers regarding the etiology of this downward shift. More study is needed to clarify whether the trend toward an earlier onset of puberty in the United States has influenced the clinical picture of acne. Additional research will help advance understanding of the spectrum of pathophysiologic changes in acne in younger pediatric patients and whether it varies from that found in individuals in whom the onset of acne occurs at approximately 12 years of age or later., (Copyright (c) 2010 Elsevier Inc. All rights reserved.)