Transforming growth factor β activates Rac1 and Cdc42Hs GTPases and the JNK pathway in skeletal muscle cells

The production of nitric oxide (NO) via the inducible form of NO synthase (iNOS) is regulated by a complex network of cytokines and endogenous hormones. Among these, transforming growth factor-beta (TGF-beta 1) is known to suppress iNOS expression and NO production by many cell types. To determine the effect of TGF-beta 1 on NO production by skeletal muscle cells, we stimulated C2C12 myocytes with interferon-gamma (IFN) and interleukin-1 (IL-1) in the presence or absence of TGF-beta 1. In contrast to findings in macrophages, TGF-beta 1 markedly enhanced NO production by skeletal muscle cells. Increases in NO production reflected significant increases in iNOS immunoreactive protein and iNOS mRNA. Elevated iNOS mRNA levels associated with TGF-beta 1 treatment were not due to an alteration in mRNA stability, but rather reflected a significantly increased transcriptional rate of the iNOS gene. These findings indicate that TGF-beta 1 enhances iNOS expression in skeletal muscle cells and suggest that the regulation of NO production by TGF-beta 1 may depend on the cell type studied.

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Transforming Growth Factor-β and Notch Signaling Mediate Stem Cell Differentiation into Smooth Muscle Cells

Stem Cells ◽

10.1002/stem.319 ◽

2010 ◽

Vol 28 (4) ◽

pp. 734-742 ◽

Cited By ~ 171

Author(s):

Kyle Kurpinski ◽

Hayley Lam ◽

Julia Chu ◽

Aijun Wang ◽

Ahra Kim ◽

...

Keyword(s):

Smooth Muscle ◽

Stem Cell ◽

Cell Differentiation ◽

Growth Factor ◽

Smooth Muscle Cells ◽

Notch Signaling ◽

Transforming Growth Factor ◽

Stem Cell Differentiation ◽

Muscle Cells ◽

Transforming Growth Factor Β

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Skeletal muscle cells express the profibrotic cytokine connective tissue growth factor (CTGF/CCN2), which induces their dedifferentiation

Journal of Cellular Physiology ◽

10.1002/jcp.21324 ◽

2008 ◽

Vol 215 (2) ◽

pp. 410-421 ◽

Cited By ~ 77

Author(s):

Cecilia Vial ◽

Lidia Miriam Zúñiga ◽

Claudio Cabello-Verrugio ◽

Pablo Cañón ◽

Ricardo Fadic ◽

...

Keyword(s):

Skeletal Muscle ◽

Growth Factor ◽

Connective Tissue ◽

Connective Tissue Growth Factor ◽

Muscle Cells ◽

Tissue Growth ◽

Skeletal Muscle Cells

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Transforming growth factor-β and myostatin signaling in skeletal muscle

Journal of Applied Physiology ◽

10.1152/japplphysiol.01091.2007 ◽

2008 ◽

Vol 104 (3) ◽

pp. 579-587 ◽

Cited By ~ 182

Author(s):

Helen D. Kollias ◽

John C. McDermott

Keyword(s):

Skeletal Muscle ◽

Growth Factor ◽

Signaling Pathway ◽

Muscle Development ◽

Cellular Proliferation ◽

Transforming Growth Factor ◽

Transforming Growth Factor Β ◽

Related Family ◽

Cytokine Milieu

The superfamily of transforming growth factor-β (TGF-β) cytokines has been shown to have profound effects on cellular proliferation, differentiation, and growth. Recently, there have been major advances in our understanding of the signaling pathway(s) conveying TGF-β signals to the nucleus to ultimately control gene expression. One tissue that is potently influenced by TGF-β superfamily signaling is skeletal muscle. Skeletal muscle ontogeny and postnatal physiology have proven to be exquisitely sensitive to the TGF-β superfamily cytokine milieu in various animal systems from mice to humans. Recently, major strides have been made in understanding the role of TGF-β and its closely related family member, myostatin, in these processes. In this overview, we will review recent advances in our understanding of the TGF-β and myostatin signaling pathways and, in particular, focus on the implications of this signaling pathway for skeletal muscle development, physiology, and pathology.

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