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J. Biol. Chem., Vol. 279, Issue 16, 15715-15718, April 16, 2004

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ACCELERATED PUBLICATIONS

Syndecan-2 Regulates Transforming Growth Factor- Signaling^*

Ligong Chen, Carmen Klass, and Anne Woods

From the Department of Cell Biology, University of Alabama at Birmingham, Birmingham, Alabama 35294 and the Department of Medicine, Emory University School of Medicine, Atlanta, Georgia 30303

Transforming growth factor- (TGF-) has multiple functions including increasing extracellular matrix deposition in fibrosis. It functions through a complex family of cell surface receptors that mediate downstream signaling. We report here that a transmembrane heparan sulfate proteoglycan, syndecan-2 (S2), can regulate TGF- signaling. S2 protein increased in the renal interstitium in diabetes and regulated TGF--mediated increased matrix deposition in vitro. Transfection of renal papillary fibroblasts with S2 or a S2 construct that has a truncated cytoplasmic domain (S2S) promoted TGF- binding and S2 core protein ectodomain directly bound TGF-. Transfection with S2 increased the amounts of type I and type II TGF- receptors (TRI and TRII), whereas S2S was much less effective. In contrast, S2S dramatically increased the level of type III TGF- receptor (TRIII), betaglycan, whereas S2 resulted in a decrease. Syndecan-2 specifically co-immunoprecipitated with betaglycan but not with TRI or TRII. This is a novel mechanism of control of TGF- action that may be important in fibrosis.

Received for publication, September 22, 2003 , and in revised form, January 30, 2004.

^* This work was supported by National Institutes of Health Grant DK54605 (to A. W.). 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 Cell Biology, University of Alabama at Birmingham, THT 946, 1530 3rd Ave. S, Birmingham, AL 35294-0006. Tel.: 205-934-1548; Fax: 205-934-7029; E-mail: anwoods{at}uab.edu.

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