Smad3 signaling is required for satellite cell function and myogenic differentiation of myoblasts.

Details

Serval ID
serval:BIB_74153695E96D
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Smad3 signaling is required for satellite cell function and myogenic differentiation of myoblasts.
Journal
Cell Research
Author(s)
Ge X., McFarlane C., Vajjala A., Lokireddy S., Ng Z.H., Tan C.K., Tan N.S., Wahli W., Sharma M., Kambadur R.
ISSN
1748-7838 (Electronic)
ISSN-L
1001-0602
Publication state
Published
Issued date
2011
Volume
21
Number
11
Pages
1591-1604
Language
english
Abstract
TGF-β and myostatin are the two most important regulators of muscle growth. Both growth factors have been shown to signal through a Smad3-dependent pathway. However to date, the role of Smad3 in muscle growth and differentiation is not investigated. Here, we demonstrate that Smad3-null mice have decreased muscle mass and pronounced skeletal muscle atrophy. Consistent with this, we also find increased protein ubiquitination and elevated levels of the ubiquitin E3 ligase MuRF1 in muscle tissue isolated from Smad3-null mice. Loss of Smad3 also led to defective satellite cell (SC) functionality. Smad3-null SCs showed reduced propensity for self-renewal, which may lead to a progressive loss of SC number. Indeed, decreased SC number was observed in skeletal muscle from Smad3-null mice showing signs of severe muscle wasting. Further in vitro analysis of primary myoblast cultures identified that Smad3-null myoblasts exhibit impaired proliferation, differentiation and fusion, resulting in the formation of atrophied myotubes. A search for the molecular mechanism revealed that loss of Smad3 results in increased myostatin expression in Smad3-null muscle and myoblasts. Given that myostatin is a negative regulator, we hypothesize that increased myostatin levels are responsible for the atrophic phenotype in Smad3-null mice. Consistent with this theory, inactivation of myostatin in Smad3-null mice rescues the muscle atrophy phenotype.
Pubmed
Web of science
Open Access
Yes
Create date
02/05/2011 9:31
Last modification date
20/08/2019 15:31
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