HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 280, Issue 9, 8079-8085, March 4, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: 280/9/8079    most recent M409647200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend 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. Social Bookmarking                      What's this?

Ultraviolet Irradiation Induces Smad7 via Induction of Transcription Factor AP-1 in Human Skin Fibroblasts^*

Taihao Quan, Tianyuan He, John J. Voorhees, and Gary J. Fisher

From the Department of Dermatology, University of Michigan Medical School, Ann Arbor, Michigan 48109-0609

Smad7 functions as an endogenous negative regulator of transforming growth factor- (TGF-)/SMAD signaling. The TGF-/SMAD pathway is a major regulator of collagen production in connective tissue. Reduced expression of SMAD7 has been reported in TGF--mediated fibrotic diseases, characterized by overproduction of collagen. Solar ultraviolet (UV) irradiation reduces collagen production by fibroblasts in human skin in vivo. We have investigated regulation of Smad7 gene expression by UV irradiation in human skin fibroblasts. UV irradiation transiently increased SMAD7 mRNA and protein levels. Induction of SMAD7 mRNA and protein was maximal within 5 h and returned to initial basal levels 24 h post-UV irradiation. UV irradiation induced Smad7 promoter-reporter activity 3-fold. The Smad7 promoter contains functional enhancer sequences that bind transcription factors SMAD3 and activator protein-1 (AP-1). UV irradiation reduced protein binding to the Smad3 enhancer and increased binding to the AP-1 enhancer. Deletion of the AP-1 binding site in the Smad7 promoter completely abolished UV stimulation of SMAD7 transcription. Deletion of the Smad3 element had no effect on UV irradiation-induced promoter activity. UV irradiation increased mRNA and protein expression of the AP-1 family members, c-Jun and c-Fos, which bound to the AP-1 element in the Smad7 promoter. Furthermore, overexpression of dominant negative c-Jun substantially reduced UV irradiation induction of SMAD7 transcription. These data demonstrate that induction of Smad7 gene expression by UV irradiation is mediated via induction of the transcription factor AP-1 in human skin fibroblasts.

Received for publication, August 23, 2004 , and in revised form, November 1, 2004.

^* This work was supported in part by the Babcock Foundation and National Institutes of Health Grant AG19364-02 (to G. J. F.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed: Dept. of Dermatology, University of Michigan Medical School, 1150 W. Medical Center Dr., Medical Science I, Rm. 6447, Ann Arbor, MI 48109-0609. Tel.: 734-763-1469; Fax: 734-647-0076; E-mail: dianemch{at}umich.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				X. Zhang, L. Zhang, H. Yang, X. Huang, H. Otu, T. A. Libermann, W. C. DeWolf, R. Khosravi-Far, and A. F. Olumi c-Fos as a Proapoptotic Agent in TRAIL-Induced Apoptosis in Prostate Cancer Cells Cancer Res., October 1, 2007; 67(19): 9425 - 9434. [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]

				P. Davoodpour and M. Landstrom 2-Methoxyestradiol-induced Apoptosis in Prostate Cancer Cells Requires Smad7 J. Biol. Chem., April 15, 2005; 280(15): 14773 - 14779. [Abstract] [Full Text] [PDF]