TY - JOUR
T1 - Relationships between transforming growth factor-β1, myostatin, and decorin
T2 - Implications for skeletal muscle fibrosis
AU - Zhu, Jinhong
AU - Li, Yong
AU - Shen, Wei
AU - Qiao, Chunping
AU - Ambrosio, Fabrisia
AU - Lavasani, Mitra
AU - Nozaki, Masahiro
AU - Branca, Maria F.
AU - Huard, Johnny
PY - 2007/8/31
Y1 - 2007/8/31
N2 - 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.
AB - 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.
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U2 - 10.1074/jbc.M704146200
DO - 10.1074/jbc.M704146200
M3 - Article
C2 - 17597062
AN - SCOPUS:34548492947
SN - 0021-9258
VL - 282
SP - 25852
EP - 25863
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 35
ER -