Details

Autor(en) / Beteiligte

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

Titel

Solar Ultraviolet Irradiation Reduces Collagen in Photoaged Human Skin by Blocking Transforming Growth Factor-β Type II Receptor/Smad Signaling

Ist Teil von

• The American journal of pathology, 2004-09, Vol.165 (3), p.741-751

Ort / Verlag

Bethesda, MD: Elsevier Inc

Erscheinungsjahr

2004

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Ultraviolet (UV) irradiation from the sun reduces production of type I procollagen (COLI), the major structural protein in human 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 the 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 II 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 in 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.