Solar ultraviolet irradiation reduces collagen in photoaged human skin by blocking transforming growth factor-β type II receptor/Smad signaling

Taihao Quan, Tianyuan He, Sewon Kang, John J. Voorhees, Gary J. Fisher

Research output: Contribution to journalArticle

Abstract

Ultraviolet (UV) irradiation from the sun reduces production of type I procollagen (COLI), the major structural protein in toman skin. This reduction is a key feature of the pathophysiology of premature skin aging (photoaging). Photoaging is the most common form of skin damage and is associated with skin carcinoma. TGF-β/Smad pathway is the major regulator of type I procollagen synthesis in human skin. We have previously reported that UV irradiation impairs transforming growth factor-β (TGF-β)/Smad signaling in mink lung epithelial cells. We have investigated the mechanism of UV irradiation impairment of the TGf-β/Smad pathway and die impact of this impairment on type I procollagen production in human skin fibroblasts, the major collagen-producing cells in skin. We report here that UV irradiation impairs TGF-β/Smad pathway in human skin by down-regulation of TGF-β type receptor (TβRII). This loss of TβRII occurs within 8 hours after UV irradiation and precedes down-regulation of type I procollagen expression in human skin, in vivo. In human skin fibroblasts, UV-induced TβRII down-regulation is mediated by transcriptional repression and results in 90% reduction of specific, cell-surface binding of TGF-β. This loss of TβRII prevents downstream activation of Smad2/3 by TGF-β, thereby reducing expression of type I procollagen. Preventing loss of TβRII by overexpression protects against UV inhibition of type I procollagen gene expression hi human skin fibroblasts. UV-induced down-regulation of TβRII, with attendant reduction of type I procollagen production, is a critical molecular mechanism in the pathophysiology of photoaging.

Original languageEnglish (US)
Pages (from-to)741-751
Number of pages11
JournalAmerican Journal of Pathology
Volume165
Issue number3
DOIs
StatePublished - Sep 2004
Externally publishedYes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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