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The role of transforming growth factor beta-extracellular matrix signaling in skeletal muscle growth and development

Li, Xuehui
http://rave.ohiolink.edu/etdc/view?acc_num=osu1216326705

Abstract Details

2008, Doctor of Philosophy, Ohio State University, Animal Sciences.
Muscle development is a highly organized process, regulated by interactions between muscle cells and their extracellular matrix (ECM) environment. The ECM through its regulation of growth factors plays a pivotal role in muscle growth and development. Transforming growth factor-β1 (TGF-β1) is a potent inhibitor of muscle cell proliferation and differentiation. Decorin, one of components in the ECM, binds to TGF-β1 and modulates muscle cell responsiveness to TGF-β1. The TGF-β1 signal is carried by Smad proteins into the cell nucleus, resulting in an inhibition of the expression of certain myogenic regulatory factors. In addition, TGF-β1 affects expression of cell β1 integrin adhesion receptor that is involved in cell adhesion and survival. However, the mechanism by which these factors interact and the signaling pathway is largely unknown. To address this mechanism, both in vitro and in vivo studies were preformed. In vitro studies showed that TGF-β1 reduced both decorin and β1 integrin expression, and altered the localization of β1 integrin in satellite cells. Decorin plays a negative role in the TGF-β1-dependent signaling pathway in terms of inhibiting satellite cell responsiveness to TGF-β1, resulting in enhanced cell proliferation and differentiation. Decreased expression of β1 integrin is likely involved in the programmed cell death or apoptotic effect of TGF-β1 on muscle cells through regulating focal adhesion kinase signaling pathway. The expression of myogenic regulatory factors, MyoD and myogenin, was inhibited by TGF-β1 through Smad3-mediated pathway, resulting in decreased satellite cell proliferation and differentiation. In vivo studies investigated the function of TGF-β1 on the expression and localization of β1 integrin and decorin during muscle formation by injection of TGF-β1 into the developing chicken embryo. In addition, the muscle cells from Low Score Normal (LSN) chicken, genetic muscle weakness, showed a different cellular responsiveness to TGF-β1 compared to the normal, which suggests a complex mechanism involved in the LSN condition. This study provides new information on the role of the TGF-β1-ECM signaling pathway in muscle growth and development, which will not only be critical to the domestic animal industries, but also benefit human health in terms of the repair and regeneration of muscle with age.
Sandra G. Velleman, PhD (Advisor)
Paul Kuber, PhD (Committee Member)
Karl Nestor, PhD (Committee Member)
Peter Reiser, PhD (Committee Member)
338 p.
Agriculture; Animals; Biology; Cellular Biology; Molecular Biology
chicken; extracellular matrix; muscle; transforming growth factor-&946; 1

Recommended Citations

Citations

  • Li, X. (2008). The role of transforming growth factor beta-extracellular matrix signaling in skeletal muscle growth and development [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1216326705

    APA Style (7th edition)

  • Li, Xuehui. The role of transforming growth factor beta-extracellular matrix signaling in skeletal muscle growth and development. 2008. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1216326705.

    MLA Style (8th edition)

  • Li, Xuehui. "The role of transforming growth factor beta-extracellular matrix signaling in skeletal muscle growth and development." Doctoral dissertation, Ohio State University, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=osu1216326705

    Chicago Manual of Style (17th edition)

osu1216326705
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© 2008, all rights reserved.
This open access ETD is published by The Ohio State University and OhioLINK.