Regulation of myostatin signaling by c-Jun N-terminal kinase in C2C12 cells

Huang, Zhiqing; Chen, Shuai; Zhang, Keying; Yu, Bing; Chen, Xiaoling; Meng, Jianghong

doi:10.1016/j.cellsig.2007.07.002

Cited by 83 publications

(61 citation statements)

References 34 publications

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“…In this study, higher myostatin level was shown to be, in part, responsible for the muscle atrophy in Smad3-null mice. This further suggests that myostatin could signal independently of Smad3 via either Smad2 or other signaling pathways, such as p38 mitogen-activated protein kinase (MAPK), c-Jun Nterminal kinase (JNK), and phosphatidylinositol 3-kinase (PI3K) pathways as shown previously [9,[39][40][41][42]. In the present manuscript, we have provided evidence to support the critical role of Smad3 in regulation of postnatal myogenesis and SC function in mice.…”

Section: Muscle Atrophy Seen In Smad3-null Muscles Could Be Due To Insupporting

confidence: 54%

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

McFarlane

Vajjala

et al. 2011

Cell Res

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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.

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Section: Muscle Atrophy Seen In Smad3-null Muscles Could Be Due To Insupporting

confidence: 54%

“…However, other signaling pathways including Smad2 are also shown to be involved in myostatin signaling [9,13,[39][40][41][42]. In this study, higher myostatin level was shown to be, in part, responsible for the muscle atrophy in Smad3-null mice.…”

Section: Muscle Atrophy Seen In Smad3-null Muscles Could Be Due To Inmentioning

confidence: 59%

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

McFarlane

Vajjala

et al. 2011

Cell Res

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“…The recent observation that the atrophy seen in Smad3 −/− muscles could be due to altered Mstn levels supports this idea (65). Mstn may signal independently of Smad3 via either Smad2 or other pathways such as the phosphatidylinositol 3-kinase Wnt and c-Jun N-terminal kinase pathways (66)(67)(68).…”

Section: Discussionmentioning

confidence: 60%

Numb-deficient satellite cells have regeneration and proliferation defects

George

Biressi

Beres

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Significance This study discloses a role for Numb in the activation and proliferation of adult muscle satellite cells and a unique function in the regulation of the muscle mass determinant Myostatin. Using two different genetic approaches to ablate Numb , one that ablated Numb in the myogenic lineage developmentally leading to reduced muscle mass. We determined that, in Numb-deficient muscle, regeneration was impaired, there was reduced stem cell proliferation, and there was an up-regulation of Myostatin. Overexpression of Numb suppressed Myostatin expression, and Myostatin-specific siRNA rescued the proliferation defect. These studies increase our knowledge of the signaling pathways involved in stem cell function and raise the possibility of regulating the Numb/Myostatin balance as a therapeutic approach to enhance muscle regeneration.

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“…TAK1 is regulated by various receptors, including members of the TGF-β receptor family. Blockade of ActRIIb, a member of the TGF-β receptor family that is able to regulate TAK1 (44,45), has been shown to increase a thermogenic gene program, including the regulation of UCP-1 in WAT and BAT (46,47), suggesting an alternative mechanism by which adipocyte-specific TAK1 deficiency may increase UCP-1 expression in WAT. Our data show that increased apoptosis in TAK1-deficient adipocytes leads to infiltration of M2-polarized macrophages expressing tyrosine hydroxylase, a rate-limiting enzyme in catecholamine biosynthesis.…”

Section: Discussionmentioning

confidence: 99%