TY - JOUR
T1 - Solar ultraviolet irradiation reduces collagen in photoaged human skin by blocking transforming growth factor-β type II receptor/Smad signaling
AU - Quan, Taihao
AU - He, Tianyuan
AU - Kang, Sewon
AU - Voorhees, John J.
AU - Fisher, Gary J.
PY - 2004/9
Y1 - 2004/9
N2 - 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.
AB - 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.
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U2 - 10.1016/S0002-9440(10)63337-8
DO - 10.1016/S0002-9440(10)63337-8
M3 - Article
C2 - 15331399
AN - SCOPUS:4344670210
SN - 0002-9440
VL - 165
SP - 741
EP - 751
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 3
ER -