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Background: Cashmere, known as "soft gold", is a highly prized fiber from Cashmere goats, produced by secondary hair follicles. Dermal papilla cells, located at the base of these follicles, regulate the proliferation and differentiation of hair matrix cells, which are essential for hair growth and cashmere formation. Recent studies emphasize the role of microRNAs (miRNAs) in controlling gene expression within these processes. Methods: This study centered on exploring the targeted regulatory interaction between miR-144 and the Lhx2 gene. Utilizing methodologies like miRNA target prediction, luciferase reporter assays, and quantitative PCR, they assessed the interplay between miR-144 and Lhx2. Dermal papilla cells derived from Cashmere goats were cultured and transfected with either miR-144 mimics or inhibitors to observe the subsequent effects on Lhx2 expression. Results: The results demonstrated that miR-144 directly targets the Lhx2 gene by binding to its mRNA, leading to a decrease in Lhx2 expression. This modulation of Lhx2 levels influenced the behavior of dermal papilla cells, affecting their ability to regulate hair matrix cell proliferation and differentiation. Consequently, the manipulation of miR-144 levels had a significant impact on the growth cycle of cashmere wool. Conclusions: The findings suggest miR-144 regulates hair follicle dynamics by targeting Lhx2, offering insights into hair growth mechanisms. This could lead to innovations in enhancing cashmere production, fleece quality, and addressing hair growth disorders. Future research may focus on adjusting miR-144 levels to optimize Lhx2 expression and promote hair follicle activity. [ABSTRACT FROM AUTHOR]

Introduction: The hair follicle (HF) is a micro-organ capable of regeneration. A HF cycle consists of an anagen, catagen and telogen. Abnormalities in the HF cycle can lead to many hair disorders such as hair loss. The pig is a good biomedical model, but there are few data on their HF cycle. The aim of this study was to classify the pig HF cycle and determine the feasibility of the pig as an animal model for human HF cycle. Methods: Skin samples from 10 different postnatal (P) days Yorkshire pigs was collected to determine the key time points of the first HF cycle in pig by H&E staining, immunofluorescence staining, q-PCR and western-blot. Results: By morphological observation and detection of markers at different stages, pig HF cycle was classified into three main periods - the first anagen until P45, catagen (P45-P85), telogen (P85-P100), and next anagen (>P100). In addition, we examined the expression of important genes AE15, CD34, Versican, Ki67 et al. related to the HF cycle at different stages of pig HF, indicating that pig and human share similarities in morphology and marker gene expression patterns of HF cycle. Discussion: Our findings will facilitate the study of HF cycle and offer researchers a suitable model for human hair research. [ABSTRACT FROM AUTHOR]

Background: The growth of secondary hair follicles (SHFs) in cashmere goats has periodic changes, including telogen, anagen, and catagen, during which proteins play important roles as the executor of life activities. Results: In this study, the skin tissues of cashmere goats at three different growth stages of SHFs were collected for proteome sequencing and validation experiments. Through protein differential expression analysis and time series analysis, FKBP prolyl isomerase 10 (FKBP10) and fibrillin 2 (FBN2) were screened as the key proteins for SHF cycle growth of cashmere goats, and albumin (ALB), collagen type I alpha 1 chain (COL1A1) and elastin (ELN) were predicted to be their interacting proteins. The results of quantitative real-time PCR (qRT- PCR), western blot, and immunohistochemistry experiments showed that the mRNA and protein expression levels of FKBP10, FBN2, COL1A1, ELN and ALB were higher in anagen and lower in telogen. They were all highly expressed in the outer root sheath of SHFs in anagen. Conclusion: FKBP10, FBN2, COL1A1, ELN, and ALB can promote the growth of SHFs in cashmere goats. This study lays the foundation for analyzing the growth cycle regulatory mechanism of SHFs in cashmere goats, and provides new ideas for further improving cashmere yield and quality. [ABSTRACT FROM AUTHOR]

Abstract Background The hair follicle is a skin accessory organ that regulates hair development, and its activity varies on a regular basis. However, the significance of metabolites in the hair follicle cycle has long been unknown. Results Targeted metabolomics was used in this investigation to reveal the expression patterns of 1903 metabolites in cashmere goat skin during anagen to telogen. A statistical analysis was used to investigate the potential associations between metabolites and the hair follicle cycle. The findings revealed clear changes in the expression patterns of metabolites at various phases and in various feeding models. The majority of metabolites (primarily amino acids, nucleotides, their metabolites, and lipids) showed downregulated expression from anagen (An) to telogen (Tn), which was associated with gene expression, protein synthesis and transport, and cell structure, which reflected, to some extent, that the cells associated with hair follicle development are active in An and apoptotic in An–Tn. It is worth mentioning that the expression of vitamin D3 and 3,3’,5-triiodo-L-thyronine decreased and then increased, which may be related to the shorter and longer duration of outdoor light, which may stimulate the hair follicle to transition from An to catagen (Cn). In the comparison of different hair follicle development stages (An, Cn, and Tn) or feeding modes (grazing and barn feeding), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that common differentially expressed metabolites (DEMs) (2’-deoxyadenosine, L-valine, 2’-deoxyuridine, riboflavin, cytidine, deoxyguanosine, L-tryptophan, and guanosine-5’-monophosphate) were enriched in ABC transporters. This finding suggested that this pathway may be involved in the hair follicle cycle. Among these DEMs, riboflavin is absorbed from food, and the expression of riboflavin and sugars (D-glucose and glycogen) in skin tissue under grazing was greater and lower than that during barn feeding, respectively, suggesting that eating patterns may also alter the hair follicle cycle. Conclusions The expression patterns of metabolites such as sugars, lipids, amino acids, and nucleotides in skin tissue affect hair follicle growth, in which 2’-deoxyadenosine, L-valine, 2’-deoxyuridine, riboflavin, cytidine, deoxyguanosine, L-tryptophan, and guanosine-5’-monophosphate may regulate the hair follicle cycle by participating in ABC transporters. Feeding practices may regulate hair follicle cycles by influencing the amount of hormones and vitamins expressed in the skin of cashmere goats.

Background: The hair follicle is a skin accessory organ that regulates hair development, and its activity varies on a regular basis. However, the significance of metabolites in the hair follicle cycle has long been unknown. Results: Targeted metabolomics was used in this investigation to reveal the expression patterns of 1903 metabolites in cashmere goat skin during anagen to telogen. A statistical analysis was used to investigate the potential associations between metabolites and the hair follicle cycle. The findings revealed clear changes in the expression patterns of metabolites at various phases and in various feeding models. The majority of metabolites (primarily amino acids, nucleotides, their metabolites, and lipids) showed downregulated expression from anagen (An) to telogen (Tn), which was associated with gene expression, protein synthesis and transport, and cell structure, which reflected, to some extent, that the cells associated with hair follicle development are active in An and apoptotic in An–Tn. It is worth mentioning that the expression of vitamin D3 and 3,3',5-triiodo-L-thyronine decreased and then increased, which may be related to the shorter and longer duration of outdoor light, which may stimulate the hair follicle to transition from An to catagen (Cn). In the comparison of different hair follicle development stages (An, Cn, and Tn) or feeding modes (grazing and barn feeding), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that common differentially expressed metabolites (DEMs) (2'-deoxyadenosine, L-valine, 2'-deoxyuridine, riboflavin, cytidine, deoxyguanosine, L-tryptophan, and guanosine-5'-monophosphate) were enriched in ABC transporters. This finding suggested that this pathway may be involved in the hair follicle cycle. Among these DEMs, riboflavin is absorbed from food, and the expression of riboflavin and sugars (D-glucose and glycogen) in skin tissue under grazing was greater and lower than that during barn feeding, respectively, suggesting that eating patterns may also alter the hair follicle cycle. Conclusions: The expression patterns of metabolites such as sugars, lipids, amino acids, and nucleotides in skin tissue affect hair follicle growth, in which 2'-deoxyadenosine, L-valine, 2'-deoxyuridine, riboflavin, cytidine, deoxyguanosine, L-tryptophan, and guanosine-5'-monophosphate may regulate the hair follicle cycle by participating in ABC transporters. Feeding practices may regulate hair follicle cycles by influencing the amount of hormones and vitamins expressed in the skin of cashmere goats. [ABSTRACT FROM AUTHOR]

MicroRNA exerts an important regulatory role in almost all the biological process, including hair follicle development in Liaoning Cashmere goat. In order to improve the Cashmere performance of goat, the regulatory role of microRNA in hair follicle cycle has drawn hotspot attention. However, the molecular mechanisms of miRNA-1-3p involved in hair follicle development are poorly understood. In this study, we found that miRNA-1-3p was less expressed in anagen stage of hair follicle cycle of Cashmere goat than that in telogen stage by using RT-qPCR and immunoblotting analysis, in contrast to the expression pattern of FGF14. The Dual-Luciferase reporter assay was employed to verify the relationship between miRNA-1-3p and FGF14. The results showed that miRNA-1-3p specifically binds to the 3′UTR of FGF14 mRNA, and FGF14 is the target gene of miR-1-3p. In conclusion, this study shows that miRNA-1-3p may regulate hair follicle development in Liaoning Cashmere goats by targeting FGF14. [ABSTRACT FROM AUTHOR]

Fibroblast growth factor 5 (FGF5) is an important molecule required for the transition from anagen to catagen phase of the mammalian hair cycle. We previously reported that Syrian hamsters harboring a 1-bp deletion in the Fgf5 gene exhibit excessive hair growth in males. Herein, we generated Fgf5 mutant mice using genome editing via oviductal nucleic acid delivery (GONAD)/improved GONAD (i-GONAD), an in vivo genome editing system used to target early embryos present in the oviductal lumen, to study gender differences in hair length in mutant mice. The two lines (Fgf5go-malc), one with a 2-bp deletion (c.552_553del) and the other with a 1-bp insertion (c.552_553insA) in exon 3 of Fgf5, were successfully established. Each mutation was predicted to disrupt a part of the FGF domain through frameshift mutation (p.Glu184ValfsX128 or p.Glu184ArgfsX128). Fgf5go-malc1 mice had heterogeneously distributed longer hairs than wild-type mice (C57BL/6J). Notably, this change was more evident in males than in females (p < 0.0001). Immunohistochemical analysis revealed the presence of FGF5 protein in the dermal papilla and outer root sheath of the hair follicles from C57BL/6J and Fgf5go-malc1 mice. Histological analysis revealed that the prolonged anagen phase might be the cause of accelerated hair growth in Fgf5go-malc1 mice. [ABSTRACT FROM AUTHOR]

Hair follicles (HFs) are organs that periodically regenerate during the growth and development of mammals. Long non-coding RNAs (lncRNAs) are non-coding RNAs with crucial roles in many biological processes. Our previous study identified that lncRNA2919 is highly expressed in catagen during the HF cycle. In this study, the in vivo rabbit model was established using intradermal injection of adenovirus-mediated lncRNA2919. The results showed that lncRNA2919 decreased HF depth and density and contributed to HF regrowth, thereby indicating that lncRNA2919 plays a negative role in HF regeneration. Moreover, methylation levels of the lncRNA2919 promoter at different HF cycle stages were detected through bisulfite sequencing. The key CpG site that negatively correlates with lncRNA2919 expression during the HF cycle was identified. 5-Aza-dc-induced demethylation upregulated lncRNA2919 expression, and the core promoter region of lncRNA2919 was verified on the basis of luciferase activity. Furthermore, we found that DNA methylation could prevent the binding of EGR1 to the lncRNA2919 promoter region, thereby affecting the transcriptional expression of lncRNA2919. Collectively, DNA methylation inhibits the transcriptional expression of lncRNA2919, which plays a vital role in the HF cycle and HF regrowth. These findings contribute to the basic theory of epigenetics in HF biology and provide references for further research in HF disease treatment and animal wool production. [ABSTRACT FROM AUTHOR]

Alopecia is a common progressive disorder associated with abnormalities of the hair follicle cycle. Hair follicles undergo cyclic phases of hair growth (anagen), regression (catagen), and rest (telogen), which are precisely regulated by various mechanisms. However, the specific mechanism associated with hair follicle cycling, which includes noncoding RNAs and regulation of competitive endogenous RNA (ceRNA) network, is still unclear. We obtained data from publicly available databases and performed real-time quantitative polymerase chain reaction validations. These analyses revealed an increase in the expression of miRNAs and a decrease in the expression of target mRNAs and lncRNAs from the anagen to telogen phase of the murine hair follicle cycle. Subsequently, we constructed the ceRNA networks and investigated their functions using enrichment analysis. Furthermore, the androgenetic alopecia (AGA) microarray data analysis revealed that several novel alopecia-related genes were identified in the ceRNA networks. Lastly, GSPT1 expression was detected using immunohistochemistry. Our analysis revealed 11 miRNAs (miR-148a-3p, miR-146a-5p, miR-200a-3p, miR-30e-5p, miR-30a-5p, miR-27a-3p, miR-143-3p, miR-27b-3p, miR-126a-3p, miR-378a-3p, and miR-22-3p), 9 target mRNAs (Atp6v1a, Cdkn1a, Gadd45a, Gspt1, Mafb, Mitf, Notch1, Plk2, and Slc7a5), and 2 target lncRNAs (Neat1 and Tug1) were differentially expressed in hair follicle cycling. The ceRNA networks were made of 12 interactive miRNA-mRNA pairs and 13 miRNA-lncRNA pairs. The functional enrichment analysis revealed the enrichment of hair growth–related signaling pathways. Additionally, GSPT1 was downregulated in androgenetic alopecia patients, possibly associated with alopecia progression. The ceRNA network identified by our analysis could be involved in regulating the hair follicle cycle.

The growth of secondary hair follicles in cashmere goats follows a seasonal cycle. Melatonin can regulate the cycle of cashmere growth. In this study, melatonin was implanted into live cashmere goats. After skin samples were collected, transcriptome sequencing and histological section observation were performed, and weighted gene co-expression network analysis (WGCNA) was used to identify key genes and establish an interaction network. A total of 14 co-expression modules were defined by WGCNA, and combined with previous analysis results, it was found that the blue module was related to the cycle of cashmere growth after melatonin implantation. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed that the first initiation of exogenous melatonin-mediated cashmere development was related mainly to the signaling pathway regulating stem cell pluripotency and to the Hippo, TGF-beta and MAPK signaling pathways. Via combined differential gene expression analyses, 6 hub genes were identified: PDGFRA, WNT5A, PPP2R1A, BMPR2, BMPR1A, and SMAD1. This study provides a foundation for further research on the mechanism by which melatonin regulates cashmere growth.

Xu Zhai,1 Meihua Gong,1,2 Yixuan Peng,1 Daping Yang1 1Department of Plastic Surgery, The 2nd Hospital of Harbin Medical University, Harbin, People’s Republic of China; 2Department of Plastic and Cosmetic Surgery, Shenzhen People’s Hospital, Second Affiliated Hospital of Jinan University Medical College, Shenzhen, People’s Republic of ChinaCorrespondence: Daping YangDepartment of Plastic Surgery, The 2nd Hospital of Harbin Medical University, Harbin, People’s Republic of ChinaTel/Fax +86-0451-86297062Email dapingyang1223@hotmail.comPurpose: To study the changes in the hair follicle cycle and related stem cells induced by photoaging to establish a mouse model of senescence in hair follicles.Methods: There were 54 C57BL6/J mice randomly divided into three groups. The UVA group and the UVB group underwent photoaging induced by UV lamps for 8 weeks. Changes in skin and the hair follicle cycle were compared by physical signs, dermoscopy, and hematoxylin and eosin and Masson’s staining in each group. Western blot, immunohistochemistry, and RT-qPCR were carried out to test canonical proteins and gene expression of the Wnt signaling pathway in the samples. Immunofluorescence was chosen to show variations in the stem cells related to the hair follicle cycle.Results: There were more gray hairs in the UVA group than the other groups (P< 0.05). Both diameter of the hair shaft and depth of hair root were significantly decreased in the UV groups (P< 0.05). Stem cells and melanocytes of the hair follicles were reduced in the UVA group. UV, especially UVB, up-regulated the expression of the Wnt signaling pathway and prolonged anagen and telogen phases in the hair follicles, compared with the control group (P< 0.05).Conclusion: By decreasing the number of stem cells related to hair follicles, UVA induces hair follicle photoaging characterized by hair follicle miniaturization and gray hairs. UV up-regulated the expression of the Wnt signaling pathway, and the hair follicle cycle was significantly prolonged by UVB.Keywords: UVA, photoaging, hair follicle cycle, HFSCs, Wnt

Cashmere goat from Inner Mongolia is an excellent local breed in China, and the related cashmere product is a kind of precious textile raw material with high price. Cashmere is generated from secondary hair follicles, which has obvious annual periodicity and includes three different stages: anagen, catagen, and telogen. Therefore, we investigated skin transcriptome data for 12 months using weighted gene co-expression network analysis (WGCNA) to explore essential modules, pathways, and genes responsible for the periodic growth and development of secondary hair follicles. A total of 17 co-expression modules were discovered by WGCNA, and there is a strong correlation between steelblue module and month (0.65, p = 3E−09), anagen (0.52, p = 1E−05), telogen (−0.6, p = 8E−08). Gene expression was generally high during late anagen to catagen (June to December), while expression was downregulated from telogen to early anagen (January–May), which is similar to the growth rule of hair follicle cycle. KEGG pathway enrichment analyses of the genes of steelblue module indicated that genes are mainly enriched in Cell cycle, Wnt signaling pathway, p53 signaling pathway and other important signal pathways. These genes were also significantly enriched in GO functional annotation of the cell cycle, microtubule movement, microtubule binding, tubulin binding, and so on. Ten genes (WIF1, WNT11, BAMBI, FZD10, NKD1, LEF1, CCND3, E2F3, CDC6, and CDC25A) were selected from these modules, and further identified as candidate biomarkers to regulate periodic development of hair follicles using qRT-PCR. The Wnt signaling pathway and Cell cycle play an important role in the periodic development of hair follicles. Ten genes were identified as essential functional molecules related to periodic development of hair follicle. These findings laid a foundation for understanding molecular mechanisms in biological functions such as hair follicle development and hair growth in cashmere goats.

Abstract Background Cashmere goat is known for its precious undercoat. Being photoperiod-dictated, cashmere growth has been studied focusing mainly on hair follicle cycle phases (anagen, catagen and telogen). An accurate molecular knowledge of the goat hair follicle cycle, disentangling gene expression changes during phases and recognizing timing boundaries, could be useful to improve cashmere goat management and ultimately cashmere production. Results To better describe goat’s hair follicle transcriptome we applied RNA-sequencing to isolated hair follicles from five Italian cashmere goats, during the anagen and catagen phase, identifying total of 214 differentially expressed genes (DEGs): 97 were up-regulated while 117 were down-regulated in catagen with respect to anagen. Gene Ontology and pathway analysis were performed. We detected 144 significant pathways spanning from estrogen, pluripotency of stem cells, thermogenesis and fatty acid metabolism that were strongly expressed during the hair follicle phases analysed. Finally, we validated promising DEGs by RT-qPCR in the same set of samples as well as in hair follicles and entire skin biopsies of another cashmere goats cohort accounting for early anagen, anagen, early catagen, and catagen phases. Conclusions As in the isolated hair follicles, some target genes were homogenously modulated during the four hair follicle phases. Ceruloplasmin (CP) and Keratin 4 (K4), confirmed their clear cut expression between growing and resting phase. In fact, K4 was almost absent in catagen phases while CP was barely expressed in anagen phases. In particular, the strong expression of K4 in early anagen makes it an eligible marker to track the beginning of a new hair cycle, and therefore defining the optimum time for cashmere harvesting.

FGF5 and FGF18 are key factors in the regulation of the hair follicle cycle. FGF5 is overexpressed during the late anagen phase and serves as a crucial regulatory factor that promotes the anagen-to-catagen transition in the hair follicle cycle. FGF18, which is overexpressed during the telogen phase, mainly regulates the hair follicle cycle by maintaining the telogen phase and inhibiting the entry of hair follicles into the anagen phase. The inhibition of FGF5 may prolong the anagen phase, whereas the inhibition of FGF18 may promote the transition of the hair follicles from the telogen phase to the anagen phase. In the present study, we used siRNA to suppress FGF5 or FGF18 expression as a way to inhibit the activity of these genes. Using qPCR, we showed that FGF5-targeting siRNA modified by cholesterol was more effective than the same siRNA bound to a cell-penetrating peptide at suppressing the expression of FGF5 both in vitro and in vivo. We then investigated the effects of the cholesterol-modified siRNA targeting either FGF5 or FGF18 on the hair follicle cycle in a depilated area of the skin on the back of mice. The cholesterol-modified siRNA, delivered by intradermal injection, effectively regulated the hair follicle cycle by inhibiting the expression of FGF5 and FGF18. More specifically, intradermal injection of a cholesterol-modified FGF5-targeted siRNA effectively prolonged the anagen phase of the hair follicles, whereas intradermal injection of the cholesterol-modified FGF18-targeted siRNA led to the mobilization of telogen follicles to enter the anagen phase earlier. The inhibitory effect of the cholesterol-modified FGF18-targeted siRNA on FGF18 expression was also evaluated for a topically applied siRNA. Topical application of a cream containing the cholesterol-modified FGF18-targeted siRNA on a depilated area of the skin of the back of mice revealed comparable inhibition of FGF18 expression with that observed for the same siRNA delivered by intradermal injection. These findings suggested that alopecia could be prevented and hair regrowth could be restored either through the intradermal injection of cholesterol-modified siRNA targeting FGF5 or FGF18 or the topical application of FGF18 siRNA.

FGF5 and FGF18 are key factors in the regulation of the hair follicle cycle. FGF5 is overexpressed during the late anagen phase and serves as a crucial regulatory factor that promotes the anagen-to-catagen transition in the hair follicle cycle. FGF18, which is overexpressed during the telogen phase, mainly regulates the hair follicle cycle by maintaining the telogen phase and inhibiting the entry of hair follicles into the anagen phase. The inhibition of FGF5 may prolong the anagen phase, whereas the inhibition of FGF18 may promote the transition of the hair follicles from the telogen phase to the anagen phase. In the present study, we used siRNA to suppress FGF5 or FGF18 expression as a way to inhibit the activity of these genes. Using qPCR, we showed that FGF5-targeting siRNA modified by cholesterol was more effective than the same siRNA bound to a cell-penetrating peptide at suppressing the expression of FGF5 both in vitro and in vivo. We then investigated the effects of the cholesterol-modified siRNA targeting either FGF5 or FGF18 on the hair follicle cycle in a depilated area of the skin on the back of mice. The cholesterol-modified siRNA, delivered by intradermal injection, effectively regulated the hair follicle cycle by inhibiting the expression of FGF5 and FGF18. More specifically, intradermal injection of a cholesterol-modified FGF5-targeted siRNA effectively prolonged the anagen phase of the hair follicles, whereas intradermal injection of the cholesterol-modified FGF18-targeted siRNA led to the mobilization of telogen follicles to enter the anagen phase earlier. The inhibitory effect of the cholesterol-modified FGF18-targeted siRNA on FGF18 expression was also evaluated for a topically applied siRNA. Topical application of a cream containing the cholesterol-modified FGF18-targeted siRNA on a depilated area of the skin of the back of mice revealed comparable inhibition of FGF18 expression with that observed for the same siRNA delivered by intradermal injection. These findings suggested that alopecia could be prevented and hair regrowth could be restored either through the intradermal injection of cholesterol-modified siRNA targeting FGF5 or FGF18 or the topical application of FGF18 siRNA. [ABSTRACT FROM AUTHOR]

MicroRNA plays an important regulatory role in the development of all organisms, including hair follicle development. In order to improve domestic cashmere yield, the role of miRNA in hair follicle cycle has become a research hotspot. However, the molecular and cellular mechanisms by which miRNA-203 regulates hair follicle development are not completely understood. In this study, we found that the relevant target genes of miRNA-203 (DDOST and NAE1) were less expressed in telogen by qPCR and Immunoblotting analysis, contrary to the expression mode of miRNA-203. The Dual-Luciferase reporter assay was used to verify the correlation between miRNA-203 and its target gene expression. The results showed that miRNA-203 specifically binds to the 3 'UTR of DDOST and NAE1, and the expression of miRNA-203 significantly down-regulates the expression of DDOST and NAE1 mRNA and protein. Therefore, this study demonstrates that miRNA-203 may regulate hair follicle development in Cashmere goats by targeting DDOST and NAE1. [ABSTRACT FROM AUTHOR]

Background: Cashmere goat is known for its precious undercoat. Being photoperiod-dictated, cashmere growth has been studied focusing mainly on hair follicle cycle phases (anagen, catagen and telogen). An accurate molecular knowledge of the goat hair follicle cycle, disentangling gene expression changes during phases and recognizing timing boundaries, could be useful to improve cashmere goat management and ultimately cashmere production. Results: To better describe goat's hair follicle transcriptome we applied RNA-sequencing to isolated hair follicles from five Italian cashmere goats, during the anagen and catagen phase, identifying total of 214 differentially expressed genes (DEGs): 97 were up-regulated while 117 were down-regulated in catagen with respect to anagen. Gene Ontology and pathway analysis were performed. We detected 144 significant pathways spanning from estrogen, pluripotency of stem cells, thermogenesis and fatty acid metabolism that were strongly expressed during the hair follicle phases analysed. Finally, we validated promising DEGs by RT-qPCR in the same set of samples as well as in hair follicles and entire skin biopsies of another cashmere goats cohort accounting for early anagen, anagen, early catagen, and catagen phases. Conclusions: As in the isolated hair follicles, some target genes were homogenously modulated during the four hair follicle phases. Ceruloplasmin (CP) and Keratin 4 (K4), confirmed their clear cut expression between growing and resting phase. In fact, K4 was almost absent in catagen phases while CP was barely expressed in anagen phases. In particular, the strong expression of K4 in early anagen makes it an eligible marker to track the beginning of a new hair cycle, and therefore defining the optimum time for cashmere harvesting. [ABSTRACT FROM AUTHOR]

Recently discovered recurrent de- and re-differentiations of mature dermal adipocytes located at the dermis-subcutis interface as well as trans-differentiation of these cells in myofibroblasts will have serious consequences for dermatology and aesthetic medicine. These processes are strongly dependent on the phase of the hair follicle cycle and should be at least involved in acne, psoriasis, wound healing, fibrosis / scarring, androgenetic alopecia, and skin aging. [ABSTRACT FROM AUTHOR]

The hair follicle (HF) cycle is a complicated and dynamic process in mammals, associated with various signaling pathways and gene expression patterns. Non-coding RNAs (ncRNAs) are RNA molecules that are not translated into proteins but are involved in the regulation of various cellular and biological processes. This study explored the relationship between ncRNAs and the HF cycle by developing a synchronization model in Angora rabbits. Transcriptome analysis was performed to investigate ncRNAs and mRNAs associated with the various stages of the HF cycle. One hundred and eleven long non-coding RNAs (lncRNAs), 247 circular RNAs (circRNAs), 97 microRNAs (miRNAs), and 1,168 mRNAs were differentially expressed during the three HF growth stages. Quantitative real-time PCR was used to validate the ncRNA transcriptome analysis results. Gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses provided information on the possible roles of ncRNAs and mRNAs during the HF cycle. In addition, lncRNA–miRNA–mRNA and circRNA–miRNA–mRNA ceRNA networks were constructed to investigate the underlying relationships between ncRNAs and mRNAs. LNC_002919 and novel_circ_0026326 were found to act as ceRNAs and participated in the regulation of the HF cycle as miR-320-3p sponges. This research comprehensively identified candidate regulatory ncRNAs during the HF cycle by transcriptome analysis, highlighting the possible association between ncRNAs and the regulation of hair growth. This study provides a basis for systematic further research and new insights on the regulation of the HF cycle.

Transforming growth factor‐β (TGF‐β) and heat shock protein 70 (HSP70) are important for the hair follicle (HF) cycle, but it is unclear whether they participate in HF regression in yak skin. In this study, we investigated the role of TGF‐β, TGF‐βRII, and HSP70 in the transition from anagen to catagen of HFs. The results showed that TGF‐β2 transcription was significantly higher than that of TGF‐β1 and TGF‐β3 in the same periods. Meanwhile, the expressions of TGF‐β2, TGF‐βRII, and caspase‐3 were higher in the catagen phase than that in mid‐anagen, and some TGF‐βRII‐positive HF cells were terminal deoxynucleotidyl transferase‐mediated deoxyuridine triphosphate‐biotin nick end labeling (TUNEL)‐positive. Moreover, the HSP70 protein levels in mid‐anagen were higher than those in late‐anagen and catagen. These results suggested that TGF‐β2 plays a major role in catagen induction in yak HFs, which might be achieved via TGF‐βRII‐mediated apoptosis in HF epithelial cells. In contrast, HSP70 might protect epithelial cells from apoptosis and ultimately inhibit HF regression. In conclusion, TGF‐β2 has positive effects, whereas HSP70 has negative effects, on catagen induction. [ABSTRACT FROM AUTHOR]

The hair follicle (HF) cycle is a complicated and dynamic process in mammals, associated with various signaling pathways and gene expression patterns. Non-coding RNAs (ncRNAs) are RNA molecules that are not translated into proteins but are involved in the regulation of various cellular and biological processes. This study explored the relationship between ncRNAs and the HF cycle by developing a synchronization model in Angora rabbits. Transcriptome analysis was performed to investigate ncRNAs and mRNAs associated with the various stages of the HF cycle. One hundred and eleven long non-coding RNAs (lncRNAs), 247 circular RNAs (circRNAs), 97 microRNAs (miRNAs), and 1,168 mRNAs were differentially expressed during the three HF growth stages. Quantitative real-time PCR was used to validate the ncRNA transcriptome analysis results. Gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses provided information on the possible roles of ncRNAs and mRNAs during the HF cycle. In addition, lncRNA–miRNA–mRNA and circRNA–miRNA–mRNA ceRNA networks were constructed to investigate the underlying relationships between ncRNAs and mRNAs. LNC_002919 and novel_circ_0026326 were found to act as ceRNAs and participated in the regulation of the HF cycle as miR-320-3p sponges. This research comprehensively identified candidate regulatory ncRNAs during the HF cycle by transcriptome analysis, highlighting the possible association between ncRNAs and the regulation of hair growth. This study provides a basis for systematic further research and new insights on the regulation of the HF cycle. [ABSTRACT FROM AUTHOR]

Hair follicles (HFs) strongly interact with adipocytes within the dermal white adipose tissue (dWAT), suggesting a strong physiological dependence on the content of immature and mature adipocytes in this layer. This content is regulated by the proliferation and differentiation of adipocyte precursors, as well as by dedifferentiation of mature existing adipocytes. Spatially, long-range interactions between HFs and dWAT involve the exchange of extracellular vesicles which are differentially released by precursors, preadipocytes, and mature adipocytes. Different exogenous factors, including light irradiation, are likely to modify the release of adipocyte-derived exosomes in dWAT, which can lead to aberrations of the HF cycle. Consequently, dWAT should be considered as a potential target for the modulation of hair growth. Highlights HFs strongly interact with adipocytes within dWAT, suggesting a strong physiological dependence on the content of immature and mature adipocytes in this layer. This content is regulated by the proliferation and differentiation of adipose precursors and preadipocytes, as well as by dedifferentiation of mature existing adipocytes leading to the production of adipocyte-derived preadipocytes. Long-range spatial interactions between HFs and dermal adipocytes involve the exchange of extracellular vesicles which are differentially released by precursors, preadipocytes, and mature adipocytes, and are likely to carry various proteomic fingerprints during different phases of the HF cycle, effectively modulating the transcriptome profile of the recipient HFs. Different exogenous factors, including light irradiation and some chemical agents, can affect immature and immature adipocytes, and are likely to modify the release of adipocyte-derived exosomes in dWAT, which can lead to aberrations of the HF cycle. Dermal adipocytes should be considered as a potential target both for the modulation of hair growth and for the removal of unwanted hair. [ABSTRACT FROM AUTHOR]

Interfollicular epidermal ( IFE) homeostasis is a major physiological process allowing maintenance of the skin barrier function. Despite progress in our understanding of stem cell populations in different hair follicle compartments, cellular mechanisms of IFE maintenance, in particular, whether a hierarchy of progenitors exists within this compartment, have remained controversial. We here used multicolour lineage tracing with Brainbow transgenic labels activated in the epidermis to track individual keratinocyte clones. Two modes of clonal progression could be observed in the adult murine dorsal skin. Clones attached to hair follicles showed rapid increase in size during the growth phase of the hair cycle. On the other hand, clones distant from hair follicles were slow cycling, but could be mobilized by a proliferative stimulus. Reinforced by mathematical modelling, these data support a model where progenitor cycling characteristics are differentially regulated in areas surrounding or away from growing hair follicles. Thus, while IFE progenitors follow a non-hierarchical mode of development, spatiotemporal control by their environment can change their potentialities, with far-reaching implications for epidermal homeostasis, wound repair and cancer development. [ABSTRACT FROM AUTHOR]

Diuse hair loss is a common reason for the aected women to visit a dermatologist. e classiation of diuse euvium type is based on the physiology of the hair follicle growth cycle. e most frequent type of diuse hair loss is telogen euvium that has many dierent causes (hormonal, drugs, trace elements det, etc.), which is sometimes diult to determine as in the case of idiopathic chronic telogen euvium. In the anagen or anagen-dystrophic euvium, the causing noxious event (chemotherapy, radiotherapy) is, usually, evident. Autoimmune based alopecia incognita could cause diagnostic diulties. A speciubtype of euvium is an androgenic alopecia of females, also called "female pattern hair loss (FPHL)" which has typical clinical picture. e treatment of diuse euvium is aimed at eliminating the underlying cause, if known. In androgenetic alopecia is a frequent choice of drugs with anti-androgenic eect. Minoxidil in a 2% solution for external application is indicated in most types of diuse euvium for its ability to prolong the growth phase of the hair cycle. Finally, it is necessary to provide psychological support for patients in order to relieve the anxiety that stems from fear of losing their hair. [ABSTRACT FROM AUTHOR]

Hair follicle offers an excellent model for systems biology and regenerative medicine. So far, the stages of hair follicle growth have been evaluated by histological examination. In this work, a noninvasive spectroscopy was proposed by measuring the diffuse reflectance of mouse skin and analyzing the melanin value. Results show that the skin diffuse reflectance was relatively high when hair follicles were at the telogen stage and at the beginning of the anagen stage, and decreased with the progression of the anagen stage. When the hair follicle entered into the catagen stage, the diffuse reflectance gradually increased. The changes in the melanin content of skin had contrary dynamics. Substages of the hair follicle cycle could be distinguished by comparing the changes in melanin value with the histological examination. This study provided a new method for noninvasive evaluation of the hair follicle stage, and should be valuable for basic and therapeutic investigations on hair regeneration. [ABSTRACT FROM AUTHOR]

Cyclosporine A (CsA) enhances hair growth through caspase-dependent pathways by retarding anagen-to-catagen phase transition in the hair follicle growth cycle. Whether apoptosis-inducing factor (AIF), a protein that induces caspase-independent apoptosis, can regulate the hair follicle cycle in response to CsA is currently unclear. Here, we show that the pro-hair growth properties of CsA are in part due to blockage of AIF nuclear translocation. We first isolate hair follicles from murine dorsal skin. We then used Western blot, immunohistochemistry and immunofluorescence to evaluate the expression and localization of AIF in hair follicles. We also determined whether modulation of AIF was responsible for the effects of CsA at the anagen-to-catagen transition. AIF was expressed in hair follicles during the anagen, catagen and telogen phases. There was significant nuclear translocation of AIF as hair follicles transitioned from anagen to late catagen phase; this was inhibited by CsA, likely due to reduced cyclophilin A expression and attenuated AIF release from mitochondria. However, we note that AIF translocation was not completely eliminated, which likely explains why the transition to catagen phase was severely retarded by CsA, rather than being completely inhibited. We speculate that blockade of the AIF signalling pathway is a critical event required for CsA-dependent promotion of hair growth in mice. The study of AIF-related signalling pathways may provide insight into hair diseases and suggest potential novel therapeutic strategies. [ABSTRACT FROM AUTHOR]

Cells undergoing programmed cell death release signals that can trigger the death of cells at remote locations.

Apoptotic cells can produce signals to instruct cells in their local environment, including ones that stimulate engulfment and proliferation. We identified a novel mode of communication by which apoptotic cells induce additional apoptosis in the same tissue. Strong induction of apoptosis in one compartment of the Drosophila wing disc causes apoptosis of cells in the other compartment, indicating that dying cells can release long-range death factors. We identified Eiger, the Drosophila tumor necrosis factor (TNF) homolog, as the signal responsible for apoptosis-induced apoptosis (AiA). Eiger is produced in apoptotic cells and, through activation of the c-Jun N-terminal kinase (JNK) pathway, is able to propagate the initial apoptotic stimulus. We also show that during coordinated cell death of hair follicle cells in mice, TNF-α is expressed in apoptotic cells and is required for normal cell death. AiA provides a mechanism to explain cohort behavior of dying cells that is seen both in normal development and under pathological conditions.

Decorin is a prototypical member of the small leucine-rich proteoglycan ( SLRP) family, which is involved in numerous biological processes. The role of decorin, as a representative SLRP, in hair follicle morphogenesis has not been elucidated. We present our initial findings on decorin expression patterns during induced murine hair follicle ( HF) cycles. It was found that decorin expression is exclusively restricted to the epidermis, outer root sheath and sebaceous glands during the anagen phase, which correlates with the upregulation of decorin mRNA and protein expression in depilated murine dorsal skin. Furthermore, we used a functional approach to investigate the effects of recombinant human decorin (rhDecorin) via cutaneous injection into HFs at various murine hair cycle stages. The local injection of rhDecorin (100 μg/ml) into the hypodermis of depilated C57BL/6 mice at anagen delayed catagen progression. In contrast, rhDecorin injection during the telogen phase caused the premature onset of anagen, as demonstrated by the assessment of the following parameters: (i) hair shaft length, (ii) follicular bulbar diameter, (iii) hair follicle cycling score and (iv) follicular phase percentage. Taken together, our results suggest that decorin may modulate follicular cycling and morphogenesis. In addition, this study also provides insight into the molecular control mechanisms governing hair follicular epithelial-mesenchymal interactions. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To analyze the dynamic expression of Wnt family member 5A (Wingless-type MMTV integration Wnt site family, member 5a) in murine hair cycle and its inhibitory effects on follicle in vivo. Methods: Situ hybridization in full-thickness skin was used to observe the change of mouse protein expression in different growth stages, and Ad-Wnt5a was injected after defeathering to observe the hair follicle growth in vivo. Results: The Wnt5a mRNA was expressed at birth, and was firstly increased then decreased along with the progress of the hair cycle. It reached the peak in advanced stage of growth cycle (P<0.05). Rhoa and β-catenin expression levels were significantly decreased in three groups. Rac2 expression was significantly up-regulated, and the expression level of Wnt5a, Shh and Frizzled2 was increased, but less significantly than group 2. Conclusions: The expression of Wnt5a mRNA is consistent with change of murine follicle cycle, and has obvious inhibitory effects on the growth of hair follicle in vivo, indicating that it is antagonistic to Wnts pathway and interferes the growth of follicle together. [Copyright &y& Elsevier]

Hair is a primary characteristic of mammals, and exerts a wide range of functions including thermoregulation, physical protection, sensory activity, and social interactions. The hair shaft consists of terminally differentiated keratinocytes that are produced by the hair follicle. Hair follicle development takes place during fetal skin development and relies on tightly regulated ectodermal-mesodermal interactions. Hair follicles form during embryonic development and, after birth, undergo recurrent cycling of growth (anagen), apoptosis-driven regression (catagen), and relative quiescence (telogen). As a functional mini-organ, the hair follicle develops in an environment with dynamic and alternating changes of diverse molecular signals. Our molecular understanding of hair follicle biology relies heavily on genetically engineered mouse models with abnormalities in hair structure, growth, and/or pigmentation and significant advances have been made toward the identification of key signaling pathways and the regulatory genes involved. In this review, the basic concepts of hair follicle, a mini-complex organ, biology will be presented and its importance in clinical applications will be summarized. [ABSTRACT FROM AUTHOR]

Activin B has been reported to promote the regeneration of hair follicles during wound healing. However, its role in the development and life cycle of hair follicles has not been elucidated.In our study, the effect of activin B on mouse hair follicles of cultured and neonatal mouse skin was investigated. In these models, PBS or activin B (5, 10 or 50 ng/ml) was applied, and hair follicle development was monitored. Hair follicle initiation and development was examined using hematoxylin and eosin staining, alkaline phosphatase activity staining, Oil Red O+ staining, and the detection of TdT-mediated dUTP-biotin nick end-labeling cell apoptosis. Activin B was found to efficiently induce the initiation of hair follicles in the skin of both cultured and neonatal mice and to promote the development of hair follicles in neonatal mouse skin. Moreover, activin-B-treated hair follicles were observed to enter the anagen stage from the telogen stage and to remain in the anagen stage. These results demonstrate that activin B promotes the initiation and development of hair follicles in mice. © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

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Background: The inhibition of fibroblast growth factor 18 (FGF18) promotes the transition of hair follicles (HFs) from the telogen phase to the anagen phase. Cucurbitacin has been shown to have a good effect in promoting hair cell growth. This study explored the potential effect of cucurbitacin on hair growth and its effect on FGF18 expression in mice., Methods: Male C57BL/6J mice were randomly divided into the following two groups: (I) the vehicle group; and (II) the cucurbitacin group. Matrix cream and cucurbitacin cream were applied to the depilated skin on the back of the vehicle group mice and the cucurbitacin group mice, respectively. On days 3, 6, 9, 12, 15, and 18, the hair growth in the depilated dorsal skin of the mice was recorded with a digital camera and a HF detector, and the HF cycle status of the mice was observed by hematoxylin and eosin (H&E) staining. In addition, the level of FGF18 messenger ribonucleic acid (mRNA) in the dorsal skin was measured on days 15 and 18 by quantitative real-time polymerase chain reaction (qRT-PCR), while the level of FGF18 protein was measured by western blot and immunofluorescence staining., Results: The dorsal skin to which the cucurbitacin cream was applied began to darken on day 6 and grew hairs on day 9, which was 3 days earlier than the dorsal skin to which the matrix cream was applied. The H&E staining revealed a transition from the telogen phase to the anagen phase 3 days earlier for the cucurbitacin cream-treated skin than the matrix cream-treated skin. In addition, the skin treated with cucurbitacin cream also showed a significant decrease in FGF18 mRNA as seen by qRT-PCR, and reduced FGF18 protein levels as detected by western blot and immunofluorescence staining compared to the skin treated with matrix cream only., Conclusions: Cucurbitacin significantly reduced the levels of FGF18 mRNA and protein in the dorsal skin of mice to accelerate the HFs to enter the anagen phase earlier, thereby promoting the regeneration of hair. Thus, cucurbitacin can be considered a new and valuable agent for the development of anti-hair loss products., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-4423/coif). All authors report that this work was supported by Infinitus (China) Co., Ltd. The authors have no other conflicts of interest to declare., (2022 Annals of Translational Medicine. All rights reserved.)

Abstract: It is well recognized that the Wnt pathway, in which β-catenin and Lef-1 are important factors, is associated with many physiological processes, including embryogenesis and postnatal development. The Wnt pathway also plays a critical role in the development of skin. It regulates the formation of the dorsal dermis and epidermal appendages in the skin and the activity of epithelial stem cells. In this study, we investigated the presence and localization of β-catenin and Lef-1 in murine hair follicles through the first postnatal month, which encompasses the first hair cycle in mice, using Western blotting and immunohistochemistry. Our results show that β-catenin and Lef-1 are expressed during all stages in a hair cycle, most strongly in the anagen and weakly in the catagen and telogen phases. The results also suggest that the β-catenin-Lef-1 complex may regulate hair follicle cycling. This process will be of considerable interest to future studies. [Copyright &y& Elsevier]

Involucrin is a structural component of the keratinocyte cornified envelope that is expressed early in the keratinocyte differentiation process. It is a component of the initial envelope scaffolding and considered as a marker for keratinocyte terminal differentiation. The expression pattern of involucrin in human scalp skin and hair follicle cycle stages is not fully explored. This study addresses this issue and tests the hypothesis that 'the expression of involucrin undergoes hair follicle cycle-dependent changes'. A total of 50 normal human scalp skin biopsies were examined (healthy females, 51-62 years) using immunofluorescence staining methods and real-time PCR analysis. In each case, 50 hair follicles were analyzed (35, 10 and 5 follicles in anagen, catagen and telogen, respectively). Involucrin was prominently expressed in the human scalp skin and hair follicles, on both gene and protein levels. The protein expression showed hair follicle cycle-associated changes i.e. a very strong expression during early and mature anagen, intermediate to strong expression during catagen and prominent decline in the telogen phase. The expression value of involucrin in both anagen and catagen was statistically significantly higher than that of telogen hair follicles ( p < 0.001). This study provides the first morphologic indication that involucrin is differentially expressed in the human scalp skin and hair follicles and reports that involucrin expression pattern undergoes hair cycle-dependent changes. The clinical ramifications of these findings are open for further investigations. [ABSTRACT FROM AUTHOR]

Abstract: Although the function of c-Myc has been clarified in many tissues, until now its expression and role in hair follicle morphogenesis and the hair cycle remains unknown. In this study we detected c-Myc expression pattern in the process of mouse hair follicle development and normal cycle. We found that during hair follicle morphogenesis, the stage-specific expression of c-Myc was detected in mouse skin and was predominantly localized to the hair follicle epithelium. c-Myc expression was also consistently found in mouse skin throughout the hair follicle cycle. Through the in vivo injection of c-Myc inhibitory peptide and c-Myc expression plasmid, we also investigated the direct effects of c-Myc on the hair follicle structures during the hair follicle cycle. Our results showed that c-Myc inhibitory peptide significantly restrained the development of anagen hair follicles, while the injection of plasmid DNA encoding c-Myc in vivo clearly promoted anagen development. Our data indicate that c-Myc may play an important role in the proliferation and differentiation of the hair follicle keratinocytes during hair follicle development. c-Myc also was shown to participate in the regulation of the mouse hair growth cycle and could promote the proliferation of the hair matrix keratinocytes as well as the differentiation of the inner root sheath. [Copyright &y& Elsevier]

Gsdm is a newly found gene family, which is restricted in its expression to the gastrointestinal tract and the skin epithelium. As a main member of the Gsdma subfamily, Gsdma3 is expressed specifically in the hair follicle of mouse skin, but its function remains largely unclear. By hematoxylin and eosin staining, we showed that Gsdma3 gene mutation caused an abnormal catagen phase with unshortened length and unshrunk structure of the hair follicle, in which the development of catagen phase was inhibited. TUNEL staining further revealed that the apoptosis of the hair follicle was obviously decreased in mutant mice. Caspase- 3 downregulation was also detected by immunofluorescence, Western blot and RT-PCR in the hair follicle of the mutant mice. After intradermal injection of Gsdma3 gene expression plasmid, apoptosis as well as Caspase- 3 expression in the hair follicle of mutant mice was enhanced, and so the catagen retardation of Gsdma3-mutant mice was rescued. Our results confirmed that Gsdma3 gene mutation interfered with catagen formation during mouse hair follicle cycle and, by upregulation of Caspase- 3 expression and promotion of apoptosis, Gsdma3 gene could play an essential role in normal catagen induction. [ABSTRACT FROM AUTHOR]

Transthyretin is a serum and cerebrospinal fluid protein synthesized early in development by the liver, choroid plexus and several other tissues. It is a carrier protein for the antioxidant vitamins, retinol, and thyroid hormones. Transthyretin helps internalize thyroxine and retinol-binding protein into cells by binding to megalin, which is a multi-ligand receptor expressed on the luminal surface of various epithelia. We investigated the expression of transthyretin and its receptor megalin in the human skin; however, their expression pattern in the hair follicle is still to be elucidated. This study addresses this issue and tests the hypothesis that 'the expression of transthyretin and megalin undergoes hair follicle cycle-dependent changes.' A total of 50 normal human scalp skin biopsies were examined (healthy females, 53-62 years) using immunofluorescence staining methods and real-time PCR. In each case, 50 hair follicles were analyzed (35, 10, and 5 follicles in anagen, catagen, and telogen, respectively). Transthyretin and megalin were prominently expressed in the human scalp skin and hair follicles, on both gene and protein levels. The concentrations of transthyretin and megalin were 0.12 and 0.03 Ul/ml, respectively, as indicated by PCR. The expression showed hair follicle cycle-associated changes i.e., strong expression during early and mature anagen, very weak expression during catagen and moderate expression during telogen. The expression values of these proteins in the anagen were statistically significantly higher than those of either catagen or telogen hair follicles ( P ≤ 0.001). This study provides the first morphologic indication that transthyretin and megalin are variably expressed in the human scalp skin and hair follicles. It also reports variations in the expression of these proteins during hair follicle cycling. The clinical ramifications of these findings are open for further investigations. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Methods in hair research: how to objectively distinguish between anagen and catagen in human hair follicle organ culture. Experimental Dermatology 2010; 19: 305–312. The organ culture of human scalp hair follicles (HFs) is the best currently available assay for hair research in the human system. In order to determine the hair growth-modulatory effects of agents in this assay, one critical read-out parameter is the assessment of whether the test agent has prolonged anagen duration or induced catagen in vitro. However, objective criteria to distinguish between anagen VI HFs and early catagen in human HF organ culture, two hair cycle stages with a deceptively similar morphology, remain to be established. Here, we develop, document and test an objective classification system that allows to distinguish between anagen VI and early catagen in organ-cultured human HFs, using both qualitative and quantitative parameters that can be generated by light microscopy or immunofluorescence. Seven qualitative classification criteria are defined that are based on assessing the morphology of the hair matrix, the dermal papilla and the distribution of pigmentary markers (melanin, gp100). These are complemented by ten quantitative parameters. We have tested this classification system by employing the clinically used topical hair growth inhibitor, eflornithine, and show that eflornithine indeed produces the expected premature catagen induction, as identified by the novel classification criteria reported here. Therefore, this classification system offers a standardized, objective and reproducible new experimental method to reliably distinguish between human anagen VI and early catagen HFs in organ culture. [ABSTRACT FROM AUTHOR]

Smad4 is the common mediator for TGFβ signals, which play important functions in many biological processes. To study the role of Smad4 in skin development and epidermal tumorigenesis, we disrupted this gene in skin using the Cre-loxP approach. We showed that absence of Smad4 blocked hair follicle differentiation and cycling, leading to a progressive hair loss of mutant (MT) mice. MT hair follicles exhibited diminished expression of Lef1, and increased proliferative cells in the outer root sheath. Additionally, the skin of MT mice exhibited increased proliferation of basal keratinocytes and epidermal hyperplasia. Furthermore, we provide evidence that the absence of Smad4 resulted in a block of both TGFβ and bone morphogenetic protein (BMP) signaling pathways, including p21, a well-known cyclin-dependent kinase inhibitor. Consequently, all MT mice developed spontaneous malignant skin tumors from 3 months to 13 months of age. The majority of tumors are malignant squamous cell carcinomas. A most notable finding is that tumorigenesis is accompanied by inactivation of phosphatase and tensin homolog deleted on chromosome 10 (Pten), activation of AKT, fast proliferation and nuclear accumulation of cyclin D1. These observations revealed the essential functions of Smad4-mediated signals in repressing skin tumor formation through the TGFβ/BMP pathway, which interacts with the Pten signaling pathway. [ABSTRACT FROM AUTHOR]

• We identified 57 DAPs in the secondary hair follicle cycle of cashmere goat. • We screened out nine keratins as candidate markers of the hair follicle cycle. • We located KRT1, KRT14, and KRT19 in hair follicles by immunofluorescence assay. Cashmere is an important economic resource for the agricultural industry. The secondary hair follicle cycle can control the yield and quality of cashmere. Therefore, to improve the yield and quality of cashmere in Liaoning cashmere goats, an understanding of the skin proteomic changes in the secondary hair follicle cycle is needed. In this study, we used a label-free proteomics approach to analyze the protein expression profile of the secondary hair follicle cycle at three stages (telogen, anagen, and catagen) in goat neck skin. Proteomics, bioinformatics, and immunofluorescence assays were employed. We identified 57 differentially abundant proteins (DAPs) and discovered that the proteins of the keratin family were highly expressed in the anagen and catagen phases. The analyses indicated that nine keratin proteins (KRT25, KRT27, KRT19, KRT10, KRT77, KRT1, KRT24, KRT14, and KRT4) can be regarded as markers of the hair follicle cycle. KRT1 was located in both the inner and outer root sheath, whereas KRT14 was located in the inner root sheath and KRT19 only in the outer sheath. Phylogenetic analysis showed that these nine keratin proteins have common evolutionary precursors, and each category has similar expression patterns. Functional enrichment analysis indicated that the estrogen and ECM-receptor interaction signaling pathways play important roles in secondary hair follicle phases/cycles. These findings provide an important resource for protein information related to cashmere goats, and the identified DAPs can be further applied to improve cashmere quality and production. [ABSTRACT FROM AUTHOR]

The development of hair follicle in cashmere goats shows significant periodic change, as with mice and humans. However, for cashmere goat with double-coat, the periodic change may be due to other regulatory molecules and signal pathways. To understand the mechanism of periodic development of hair follicle, we performed a weighted gene coexpression network analysis (WGCNA) to mine key genes and establish an interaction network by utilizing the NCBI public dataset. Ten coexpression modules, including 7689 protein-coding genes, were constructed by WGCNA, six of which are considered to be significantly related to the development of the hair follicle cycle. A functional enrichment analysis for each model showed that they are closely related to ECM- receptor interaction, focal adhesion, PI3K-Akt signaling pathway, estrogen signaling pathway, and so on. Combined with the analysis of differential expressed genes, 12 hub genes from coexpression modules were selected as candidate markers, i.e., COL1A1, C1QTNF6, COL1A2, AQP3, KRTAP3-1, KRTAP11-1, FA2H, NDUFS5, DERL2, MRPL14, ANTKMT and XAB2, which might be applied to improve cashmere production. [ABSTRACT FROM AUTHOR]