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

J. Biol. Chem., Vol. 282, Issue 35, 25852-25863, August 31, 2007

This Article Full Text Full Text (PDF) All Versions of this Article: 282/35/25852    most recent M704146200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted 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 Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zhu, J. Articles by Huard, J. Search for Related Content PubMed PubMed Citation Articles by Zhu, J. Articles by Huard, J. Social Bookmarking                      What's this?

Relationships between Transforming Growth Factor-1, Myostatin, and Decorin

IMPLICATIONS FOR SKELETAL MUSCLE FIBROSIS^*

Jinhong Zhu¹, Yong Li^¶||1, Wei Shen, Chunping Qiao^¶, Fabrisia Ambrosio^**, Mitra Lavasani, Masahiro Nozaki^¶, Maria F. Branca, and Johnny Huard^¶2

From the Stem Cell Research Center, Children's Hospital of Pittsburgh, Rangos Research Center, Pittsburgh, Pennsylvania 15213-2583, the Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, the ^¶Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, the ^||Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, and the ^**Department of Physical Medicine and Rehabilitation, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213-200

Recent studies have shown that myostatin, first identified as a negative regulator of skeletal muscle growth, may also be involved in the formation of fibrosis within skeletal muscle. In this study, we further explored the potential role of myostatin in skeletal muscle fibrosis, as well as its interaction with both transforming growth factor-1 and decorin. We discovered that myostatin stimulated fibroblast proliferation in vitro and induced its differentiation into myofibroblasts. We further found that transforming growth factor-1 stimulated myostatin expression, and conversely, myostatin stimulated transforming growth factor-1 secretion in C2C12 myoblasts. Decorin, a small leucine-rich proteoglycan, was found to neutralize the effects of myostatin in both fibroblasts and myoblasts. Moreover, decorin up-regulated the expression of follistatin, an antagonist of myostatin. The results of in vivo experiments showed that myostatin knock-out mice developed significantly less fibrosis and displayed better skeletal muscle regeneration when compared with wild-type mice at 2 and 4 weeks following gastrocnemius muscle laceration injury. In wild-type mice, we found that transforming growth factor-1 and myostatin co-localize in myofibers in the early stages of injury. Recombinant myostatin protein stimulated myofibers to express transforming growth factor-1 in skeletal muscles at early time points following injection. In summary, these findings define a fibrogenic property of myostatin and suggest the existence of co-regulatory relationships between transforming growth factor-1, myostatin, and decorin.

Received for publication, May 21, 2007

^* This work was supported by National Institutes of Health Grant AR47973, the Department of Defense Grant W81XWH-06-1-04-06), the Henry J. Mankin and Jean W. Donaldson endowed Chairs, and the Hirtzel Foundation. 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 Both authors contributed equally to this work.

² To whom correspondence should be addressed: Stem Cell Research Center, Children's Hospital of Pittsburgh, 4100 Rangos Research Center, 3460 Fifth Ave., Pittsburgh, PA 15213-2583. Tel.: 412-692-7801; Fax: 412-692-7095; E-mail: jhuard{at}pitt.edu.

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

This article has been cited by other articles:

				J. N Artaza and K. C Norris Vitamin D reduces the expression of collagen and key profibrotic factors by inducing an antifibrotic phenotype in mesenchymal multipotent cells J. Endocrinol., February 1, 2009; 200(2): 207 - 221. [Abstract] [Full Text] [PDF]

				M. Nozaki, Y. Li, J. Zhu, F. Ambrosio, K. Uehara, F. H. Fu, and J. Huard Improved Muscle Healing After Contusion Injury by the Inhibitory Effect of Suramin on Myostatin, a Negative Regulator of Muscle Growth Am. J. Sports Med., December 1, 2008; 36(12): 2354 - 2362. [Abstract] [Full Text] [PDF]

				B. D. Rodgers and D. K. Garikipati Clinical, Agricultural, and Evolutionary Biology of Myostatin: A Comparative Review Endocr. Rev., August 1, 2008; 29(5): 513 - 534. [Abstract] [Full Text] [PDF]

				Z. B. Li, H. D. Kollias, and K. R. Wagner Myostatin Directly Regulates Skeletal Muscle Fibrosis J. Biol. Chem., July 11, 2008; 283(28): 19371 - 19378. [Abstract] [Full Text] [PDF]

				C. L. Mendias, K. I. Bakhurin, and J. A. Faulkner Tendons of myostatin-deficient mice are small, brittle, and hypocellular PNAS, January 8, 2008; 105(1): 388 - 393. [Abstract] [Full Text] [PDF]

				L. H. Jorgensen, C. H. Jensen, U. M. Wewer, and H. D. Schroder Transgenic Overexpression of ADAM12 Suppresses Muscle Regeneration and Aggravates Dystrophy in Aged mdx Mice Am. J. Pathol., November 1, 2007; 171(5): 1599 - 1607. [Abstract] [Full Text] [PDF]