Myostatin signaling through Smad2, Smad3 and Smad4 is regulated by the inhibitory Smad7 by a negative feedback mechanism

Zhu, Xiangyang; Topouzis, Stavros; Liang, Li-Fang; Stotish, Ronald L.

doi:10.1016/j.cyto.2004.03.007

Cited by 199 publications

(138 citation statements)

References 42 publications

Supporting

Mentioning

128

Contrasting

Unclassified

Order By: Relevance

“…As members of the TGF-␤ superfamily, TGF-␤1 and MSTN share many similarities in structure, signaling pathway, and function (52,53). It has also been shown that TGF-␤1 plays a critical role in skeletal muscle fibrosis after injury (20, 26 -32).…”

Section: Discussionmentioning

confidence: 99%

Relationships between Transforming Growth Factor-β1, Myostatin, and Decorin

Zhu

Shen

et al. 2007

Journal of Biological Chemistry

245

217

View full text Add to dashboard Cite

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-␤1 and decorin. We discovered that myostatin stimulated fibroblast proliferation in vitro and induced its differentiation into myofibroblasts. We further found that transforming growth factor-␤1 stimulated myostatin expression, and conversely, myostatin stimulated transforming growth factor-␤1 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-␤1 and myostatin colocalize in myofibers in the early stages of injury. Recombinant myostatin protein stimulated myofibers to express transforming growth factor-␤1 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-␤1, myostatin, and decorin.

show abstract

Section: Discussionmentioning

confidence: 99%

Relationships between Transforming Growth Factor-β1, Myostatin, and Decorin

Zhu

Shen

et al. 2007

Journal of Biological Chemistry

245

217

View full text Add to dashboard Cite

show abstract

“…The mature myostatin dimer acts through activin type II receptor ActRIIB and to a lesser extent ActRIIA 21. The signalling involves the phosphorylation of Smad2/3 transcription factors 24, 25, and the inhibition of the PI3K/Akt pathway 26, 27. Myostatin was shown to up‐regulate the expression of p21(Waf1/Cip1), thus preventing the progression of myoblasts from the G1‐ to S‐phase of the cell cycle 28.…”

mentioning

confidence: 99%

Syndecan‐4 influences mammalian myoblast proliferation by modulating myostatin signalling and G1/S transition

et al. 2018

View full text Add to dashboard Cite

Myostatin, a TGF‐β superfamily member, is a negative regulator of muscle growth. Here we describe how myostatin activity is regulated by syndecan‐4, a ubiquitous transmembrane heparan sulfate proteoglycan. During muscle regeneration the levels of both syndecan‐4 and promyostatin decline gradually after a sharp increase, concurrently with the release of mature myostatin. Promyostatin and syndecan‐4 co‐immunoprecipitate, and the interaction is heparinase‐sensitive. ShRNA‐mediated silencing of syndecan‐4 reduces C2C12 myoblast proliferation via blocking the progression from G1‐ to S‐phase of the cell cycle, which is accompanied by elevated levels of myostatin and p21(Waf1/Cip1), and decreases in cyclin E and cyclin D1 expression. Our results suggest that syndecan‐4 functions as a reservoir for promyostatin regulating the local bioavailability of mature myostatin.

show abstract

“…TEAD binds to the so-called MCAT elements (muscle C, A, and T; 5=-CATTCC-3=) in musclespecific genes such as that for myogenin (38). Although SMAD2 and -3, which are TAZ interactors, mediate the inhibitory signal of myostatin in muscle cells (39), TAZ is overall regarded as a myogenesis-promoting factor. This makes a sharp contrast with YAP1, whose activation induces muscle atrophy (40,41).…”

mentioning

confidence: 99%

Screening with a Novel Cell-Based Assay for TAZ Activators Identifies a Compound That Enhances Myogenesis in C2C12 Cells and Facilitates Muscle Repair in a Muscle Injury Model

Yang

Nakagawa

Sarkar

et al. 2014

Molecular and Cellular Biology

View full text Add to dashboard Cite

The transcriptional coactivator with a PDZ-binding motif (TAZ) cooperates with various transcriptional factors and plays various roles. Immortalized human mammalian epithelial MCF10A cells form spheres when TAZ is overexpressed and activated. We developed a cell-based assay using sphere formation by TAZ-expressing MCF10A cells as a readout to screen 18,458 chemical compounds for TAZ activators. Fifty compounds were obtained, and 47 were confirmed to activate the TAZ-dependent TEADresponsive reporter activity in HEK293 cells. We used the derived subset of compounds as a TAZ activator candidate minilibrary and searched for compounds that promote myogenesis in mouse C2C12 myoblast cells. In this study, we focused on one compound, IBS008738. IBS008738 stabilizes TAZ, increases the unphosphorylated TAZ level, enhances the association of MyoD with the myogenin promoter, upregulates MyoD-dependent gene transcription, and competes with myostatin in C2C12 cells. TAZ knockdown verifies that the effect of IBS008738 depends on endogenous TAZ in C2C12 cells. IBS008738 facilitates muscle repair in cardiotoxin-induced muscle injury and prevents dexamethasone-induced muscle atrophy. Thus, this cell-based assay is useful to identify TAZ activators with a variety of cellular outputs. Our findings also support the idea that TAZ is a potential therapeutic target for muscle atrophy.

show abstract

Myostatin signaling through Smad2, Smad3 and Smad4 is regulated by the inhibitory Smad7 by a negative feedback mechanism

Cited by 199 publications

References 42 publications

Relationships between Transforming Growth Factor-β1, Myostatin, and Decorin

Relationships between Transforming Growth Factor-β1, Myostatin, and Decorin

Syndecan‐4 influences mammalian myoblast proliferation by modulating myostatin signalling and G1/S transition

Screening with a Novel Cell-Based Assay for TAZ Activators Identifies a Compound That Enhances Myogenesis in C2C12 Cells and Facilitates Muscle Repair in a Muscle Injury Model

Contact Info

Product

Resources

About