This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Quan, T. Articles by Fisher, G. J. Search for Related Content PubMed PubMed Citation Articles by Quan, T. Articles by Fisher, G. J.

(American Journal of Pathology. 2004;165:741-751.)
© 2004 American Society for Investigative Pathology

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

From the Department of Dermatology, University of Michigan Medical School, Ann Arbor, Michigan

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-ß/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-ß (TGF-ß)/Smad signaling in mink lung epithelial cells. We have investigated the mechanism of UV irradiation impairment of the TGF-ß/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-ß/Smad pathway in human skin by down-regulation of TGF-ß type II receptor (TßRII). This loss of TßRII 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 TßRII down-regulation is mediated by transcriptional repression and results in 90% reduction of specific, cell-surface binding of TGF-ß. This loss of TßRII prevents downstream activation of Smad2/3 by TGF-ß, thereby reducing expression of type I procollagen. Preventing loss of TßRII by overexpression protects against UV inhibition of type I procollagen gene expression in human skin fibroblasts. UV-induced down-regulation of TßRII, with attendant reduction of type I procollagen production, is a critical molecular mechanism in the pathophysiology of photoaging.

This article has been cited by other articles:

				G. Dai, T. Freudenberger, P. Zipper, A. Melchior, S. Grether-Beck, B. Rabausch, J. de Groot, S. Twarock, H. Hanenberg, B. Homey, et al. Chronic Ultraviolet B Irradiation Causes Loss of Hyaluronic Acid from Mouse Dermis Because of Down-Regulation of Hyaluronic Acid Synthases Am. J. Pathol., November 1, 2007; 171(5): 1451 - 1461. [Abstract] [Full Text] [PDF]

				R. Kafi, H. S. R. Kwak, W. E. Schumacher, S. Cho, V. N. Hanft, T. A. Hamilton, A. L. King, J. D. Neal, J. Varani, G. J. Fisher, et al. Improvement of Naturally Aged Skin With Vitamin A (Retinol) Arch Dermatol, May 1, 2007; 143(5): 606 - 612. [Abstract] [Full Text] [PDF]

				T. Quan, T. He, Y. Shao, L. Lin, S. Kang, J. J. Voorhees, and G. J. Fisher Elevated Cysteine-Rich 61 Mediates Aberrant Collagen Homeostasis in Chronologically Aged and Photoaged Human Skin Am. J. Pathol., August 1, 2006; 169(2): 482 - 490. [Abstract] [Full Text] [PDF]

				T. Quan, T. He, J. J. Voorhees, and G. J. Fisher Ultraviolet Irradiation Induces Smad7 via Induction of Transcription Factor AP-1 in Human Skin Fibroblasts J. Biol. Chem., March 4, 2005; 280(9): 8079 - 8085. [Abstract] [Full Text] [PDF]

				Papers of Note Sci. Aging Knowl. Environ., September 8, 2004; 2004(36): nw35 - nw35. [Full Text]