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Summary: Background: Atopic dermatitis (AD) is a common, chronic, severely pruritic, eczematous skin disease that seriously deteriorates the quality of life of patients. Scratching is a cardinal symptom of AD. Although the vicious itch–scratch cycle continues and aggravates skin barrier dysfunction in AD, how scratching induces skin barrier dysfunction through tight junctions remains unclear. Aim: To study the effect of scratching on tight junctions in the itch–scratch cycle. Methods: Scratching behaviour and skin barrier dysfunction on the neck and back in an AD mouse model were assessed. The expression of tight junction proteins was compared between the neck and back mice, and the mechanisms underlying the involvement of Akt/CLDN1 pathways in this process were explored. Results: We used oxazolone to induce AD on the neck or back of mice. There was significantly more scratching behaviour and more pronounced skin barrier dysfunction with the neck than with the back. Downregulation of claudin‐1 (CLDN1) and upregulation of Akt phosphorylation in skin were well correlated with scratching behaviour in this AD model. Furthermore, SC79, an agonist of Akt phosphorylation, could downregulate CLDN1 expression in HaCaT cells. An antagonist of Akt phosphorylation (LY294002) was used to treat the AD mice; this treatment rescued CLDN1 expression through inhibiting Akt phosphorylation in skin, and importantly, also inhibited the scratching behaviour induced by AD. Conclusion: The results reveal the underlying mechanism of tight junction damage promoted by scratching in the itch–scratch cycle of AD, and opens a new avenue to pruritus management in AD, through Akt antagonists. [ABSTRACT FROM AUTHOR]

Background Symmetrical acrokeratoderma ( SAK) is characterized by brown to black hyperkeratotic patches on acral regions. Although epidermal hyperkeratosis and acanthosis are consistent pathological changes, the nature of epidermal hyperplasia is unknown. Aim To evaluate epidermal proliferation and differentiation and melanocytic density in skin lesions of SAK. Methods Expression of keratin 10 (K10), K14, K16, involucrin, filaggrin, Ki-67, and Melan-A was detected by immunohistochemistry in eight patients with SAK, seven patients with ichthyosis vulgaris ( IV) and six healthy controls ( HCs). Results Expression of K14, K16, involucrin and filaggrin was upregulated in patients with SAK compared with patients with IV and the HCs ( P < 0.01-0.05), but K10 expression was similar for the three groups ( P > 0.05). Numbers of Ki-67+ and Melan-A+ cells were higher in patients with SAK than in patients with IV and the HCs ( P < 0.05). Conclusions These results demonstrate that excessive keratinocyte proliferation and abnormal differentiation contribute to epidermal hyperplasia, while melanocytic proliferation is responsible for the pigmented lesions in SAK. [ABSTRACT FROM AUTHOR]

Six cases of eruptive vellus hair cysts ( EVHC) were evaluated for histopathology and the immunohistochemical profile of Ki-67 and four keratins ( K10, K14, K17 and K19). The pathological hallmark of EVHC was the existence of vellus hair shafts within the cystic cavity, but atypical pathological changes included two or three cysts and a foreign-body granuloma in three cases. Our results demonstrate that atypical pathological changes are not uncommon in EVHC, and indicate that based on keratin expression, it is likely that EVHC is derived from the infrainfundibulum and sebaceous duct. [ABSTRACT FROM AUTHOR]

Progressive symmetrical erythrokeratodermia (PSEK) is a rare inherited cornification disorder characterized by symmetrical erythematous hyperkeratotic plaques. The genetic basis for PSEK is not clear. PSEK shares many clinical features with erythrokeratodermia variabilis (EKV), which is associated with mutations in genes coding for gap junction beta ( GJB) 3 and 4. A mutation in the loricrin gene ( LOR) was found in patients with PSEK, who were members of a family with Vohwinkel syndrome. It would therefore be of interest to determine if PSEK is also caused by mutations in these genes. To examine the mutation status of GJB3, GJB4 and LOR in patients with PSEK and in control subjects. Genomic DNA samples from 25 patients with PSEK and 56 healthy controls were examined by sequencing analysis of the coding sequences of GJB3, GJB4 and LOR. There were no mutations found in any of these three genes. PSEK is a disorder distinct from EKV, and the true pathogenesis of PSEK remains unknown. [ABSTRACT FROM AUTHOR]

Disseminated superficial porokeratosis (DSP) is an autosomal dominant epidermal keratinization disorder. The genetic basis for DSP has not been clearly elucidated. We previously mapped the locus for DSP to a large region (5.7 Mb) at 18p11.3 in a four-generation Chinese family with DSP, but no gene responsible for porokeratosis has been identified to date. To narrow the critical region for DSP, thereby facilitating the identification of this disease gene and possibly leading to an understanding of the pathogenesis of porokeratosis, genotyping was performed on the same Chinese family with DSP using nine heterozygous single-nucleotide polymorphism markers at 18p11.3. We found the locus of DSP to be located within a 2.7 Mb region between markers rs58085394 and rs238533. Our study provides a map location for isolation of a gene causing DSP. [ABSTRACT FROM AUTHOR]

Background. Accelerating wound healing is always accompanied by excessive scar formation. The focus in chronic wounds has been promoting the proliferation of tissue repair cells while decreasing collagen deposition. Smad3 null mice display more rapid wound closure and reduced scar formation. We hypothesized that c-Ski, acting as a co-repressor of transforming growth factor-β1/Smad3 in epithelial cells and as a complicated regulator of embryo fibroblast proliferation, may play such a role through modulation of skin fibroblast function. Aim. To investigate the effect of c-Ski on skin fibroblast proliferation, cell-cycle progression, type I collagen secretion and myofibroblast differentiation. The potential involvement of Smad3 was also investigated. Methods. Cultured rat skin fibroblasts were used. Immunocytochemistry and reverse transcription (RT)-PCR was used to examine the localization and expression of c-Ski. Plasmid transfection technology was used to produce c-Ski or/and Smad3 overexpression. Cell proliferation was analysed by 5-bromo-2-deoxyuridine incorporation; cell cycle by fluorescence-activated cell sorting; type I collagen expression by immunocytochemistry, RT-PCR and western blotting; and myofibroblast differentiation by western blotting. Results. c-Ski was expressed in cultured skin fibroblasts. Overexpression of c-Ski was able to promote skin fibroblast proliferation and accelerate cell-cycle progression through inhibiting Smad3 activity. It also decreased type I collagen protein and mRNA expression through inhibiting Smad3 activity. It did not affect fibroblast–myofibroblast differentiation. Conclusions. Because of the important role of fibroblast proliferation and collagen secretion in tissue repair and scar formation, we speculate that c-Ski may be a new candidate molecule for accelerating wound healing and decreasing scar formation. [ABSTRACT FROM AUTHOR]