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J. Biol. Chem., Vol. 283, Issue 38, 25879-25886, September 19, 2008

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Faculty of 1000 *Recommended* - FREE!

Collagen Fibril Formation

A NEW TARGET TO LIMIT FIBROSIS^*

Hye Jin Chung, Andrzej Steplewski, Kee Yang Chung, Jouni Uitto, and Andrzej Fertala¹

From the Department of Dermatology and Cutaneous Biology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107 and Department of Dermatology and Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, 120-752, South Korea

We present a concept for reducing formation of fibrotic deposits by inhibiting self-assembly of collagen molecules into fibrils, a main component of fibrotic lesions. Employing monoclonal antibodies that bind to the telopeptide region of a collagen molecule, we found that blocking telopeptide-mediated collagen/collagen interactions reduces the amount of collagen fibrils accumulated in vitro and in keloid-like organotypic constructs. We conclude that inhibiting extracellular steps of the fibrotic process provides a novel approach to limit fibrosis in a number of tissues and organs.

Received for publication, June 3, 2008 , and in revised form, July 15, 2008.

^* This work was supported, in whole or in part, by National Institutes of Health Grants R01AR048544 and R01AR049537 (to A. F.) and R01AR41439 (to J. U.). 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.

¹ To whom correspondence should be addressed: Dept. of Dermatology and Cutaneous Biology, Jefferson Medical College, Thomas Jefferson University, BLSB, Rm. 424, 233 S. 10th St., Philadelphia, PA 19107. Tel.: 215-503-0113; Fax: 215-503-5788; E-mail: andrzej.fertala{at}jefferson.edu.

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