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Relationships between transforming growth factor-β1, myostatin, and decorin: Implications for skeletal muscle fibrosis

Zhu, J and Li, Y and Shen, W and Qiao, C and Ambrosio, F and Lavasani, M and Nozaki, M and Branca, MF and Huard, J (2007) Relationships between transforming growth factor-β1, myostatin, and decorin: Implications for skeletal muscle fibrosis. Journal of Biological Chemistry, 282 (35). 25852 - 25863. ISSN 0021-9258

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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-β1 and decorin. We discovered that myostatin stimulated fibroblast proliferation in vitro and induced its differentiation into myofibroblasts. We further found that transforming growth factor-β1 stimulated myostatin expression, and conversely, myostatin stimulated transforming growth factor-β1 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-β1 and myostatin colocalize in myofibers in the early stages of injury. Recombinant myostatin protein stimulated myofibers to express transforming growth factor-β1 in skeletal muscles at early time points following injection. In summary, these findings define a fibrogenic property of myostatin and suggest the existence of coregulatory relationships between transforming growth factor-β1, myostatin, and decorin. © 2007 by The American Society for Biochemistry and Molecular Biology, Inc.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Zhu, J
Li, Y
Shen, W
Qiao, C
Ambrosio, Ffaa7@pitt.eduFAA7
Lavasani, M
Nozaki, M
Branca, MF
Huard, J
Centers: Other Centers, Institutes, Offices, or Units > Stem Cell Research Center
Date: 31 August 2007
Date Type: Publication
Journal or Publication Title: Journal of Biological Chemistry
Volume: 282
Number: 35
Page Range: 25852 - 25863
DOI or Unique Handle: 10.1074/jbc.m704146200
Schools and Programs: School of Medicine > Orthopaedic Surgery
School of Medicine > Pathology
School of Medicine > Physical Medicine and Rehabilitation
Swanson School of Engineering > Bioengineering
Refereed: Yes
ISSN: 0021-9258
MeSH Headings: Animals; Cell Differentiation--drug effects; Cell Proliferation--drug effects; Decorin; Extracellular Matrix Proteins--metabolism; Extracellular Matrix Proteins--pharmacology; Female; Fibroblasts--metabolism; Fibroblasts--pathology; Fibrosis; Follistatin--biosynthesis; Mice; Muscle Fibers, Skeletal--metabolism; Muscle Fibers, Skeletal--pathology; Muscle, Skeletal--injuries; Muscle, Skeletal--metabolism; Muscle, Skeletal--pathology; Muscular Diseases--metabolism; Muscular Diseases--pathology; Myoblasts--metabolism; Myoblasts--pathology; Myostatin; NIH 3T3 Cells; Proteoglycans--metabolism; Proteoglycans--pharmacology; Recombinant Proteins--metabolism; Recombinant Proteins--pharmacology; Transforming Growth Factor beta--antagonists & inhibitors; Transforming Growth Factor beta--deficiency; Transforming Growth Factor beta--metabolism; Transforming Growth Factor beta--pharmacology; Transforming Growth Factor beta1--metabolism; Transforming Growth Factor beta1--pharmacology
PubMed ID: 17597062
Date Deposited: 09 Jun 2014 14:43
Last Modified: 13 Oct 2017 22:56


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