To Control Site-Specific Skin Gene Expression, Autocrine Mimics Paracrine Canonical Wnt Signaling and Is Activated Ectopically in Skin Disease.

Despite similar components, the heterogeneity of skin characteristics across the human body is enormous. It is classically believed that site-specific fibroblasts in the dermis control postnatal skin identity by modulating the behavior of the surface-overlying keratinocytes in the epidermis. To begin testing this hypothesis, we characterized the gene expression differences between volar (ventral; palmoplantar) and nonvolar (dorsal) human skin. We show that KERATIN 9 (KRT9) is the most uniquely enriched transcript in volar skin, consistent with its etiology in genetic diseases of the palms and soles. In addition, ectopic KRT9 expression is selectively activated by volar fibroblasts. However, KRT9 expression occurs in the absence of all fibroblasts, although not to the maximal levels induced by fibroblasts. Through gain-of-function and loss-of-function experiments, we demonstrate that the mechanism is through overlapping paracrine or autocrine canonical WNT-ß-catenin signaling in each respective context. Finally, as an in vivo example of ectopic expression of KRT9 independent of volar fibroblasts, we demonstrate that in the human skin disease lichen simplex chronicus, WNT5a and KRT9 are robustly activated outside of volar sites. These results highlight the complexities of site-specific gene expression and its disruption in skin disease.

High prevalence of stump dermatoses 38 years or more after amputation.

OBJECTIVE: To highlight the prevalence and impact of skin disease at the stump site in patients who have undergone amputation. DESIGN: A cross-sectional health questionnaire of Vietnam War veterans with stump dermatoses at least 38 years after major limb amputation. SETTING: A research registry of veterans with combat-related amputations who agreed to participate. PARTICIPANTS: Recruitment began January 1, 2006, and ended December 31, 2009, with a registry of 416 veterans. MAIN OUTCOME MEASURES: Results of a self-reported 35-item questionnaire. Participants were later contacted by telephone or asked to complete a Web survey. RESULTS: Of the 247 veterans, 119 (48.2%) reported at least 1 skin problem within the preceding year. The most common were skin breakdown (25.2%), rash (21.8%), and abrasion (21.0%). In addition, 25.2% experienced skin problems more than 50% of the time, and 37.1% had to alter or replace their prosthesis. Stump dermatoses limited or prevented prosthesis use in the preceding year for 55.6% and caused pain or discomfort at the stump site in 61.5%. CONCLUSIONS: More than 38 years after major limb amputation, skin complications at the stump site continue to cause significant morbidities and contribute to prosthesis abandonment. The high prevalence of stump dermatoses stresses the importance of disease prevention, early management, and advanced treatment of skin disease.