Am J Physiol Endocrinol Metab.; co-auth W Wahli

Am J Physiol Endocrinol Metab. 2012 Apr 24. [Epub ahead of print]

Lack of Smad3 signaling leads to impaired skeletal muscle regeneration.


1Nanyang Technological University.


Smad3 is a key intracellular signaling mediator for both TGF-β and Myostatin, two major regulators of skeletal muscle growth. Previous published work has revealed pronounced muscle atrophy together with impaired Satellite Cell (SC) functionality in Smad3-null muscles. In the present study, we have further validated a role for Smad3 signaling in skeletal muscle regeneration. Here, we show that Smad3-null mice had incomplete recovery of muscle weight and myofiber size after muscle injury. Histological/Immunohistochemical analysis suggested impaired inflammatory response and reduced number of activated myoblasts during the early stages of muscle regeneration in the M. tibialis anterior muscle of Smad3-null mice. Nascent myofibers formed after muscle injury were also reduced in number. Moreover, Smad3-null regenerated muscle had decreased oxidative enzyme activity and impaired mitochondrial biogenesis, evident by the down-regulation of the gene encoding TFAM, a master regulator of mitochondrial biogenesis. Consistent with known Smad3 function, reduced fibrotic tissue formation was also seen in regenerated Smad3-null muscle. In conclusion, Smad3 deficiency leads to impaired muscle regeneration, which underscores an essential role of Smad3 in post-natal myogenesis. Given the negative role of Myostatin during muscle regeneration, the increased expression of Myostatin observed in Smad3-null muscle may contribute to the regeneration defects.

PMID : 22535746 [PubMed – as supplied by publisher]