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Serum Response Factor (SRF)-Dependent Signaling in Regenerating, Hypertrophied, and Pahological Skeletal Muscle

Serum Response Factor (SRF)-Dependent Signaling in Regenerating, Hypertrophied, and Pahological... Serum response factor (SRF) is an ubiquitously expressed member of the MADS (MCM1, Agamous, Deficiens, SRF) box transcription factor family, sharing a highly conserved DNA-binding/dimerization domain, which binds the core sequence of SRE/CArG boxes (CC (A/T)6 GG). In addition, SRF is as well a widely expressed transcription factor involved in orchestrating disparate programs of gene expression linked to differentiation and cellular growth in smooth, cardiac, and skeletal muscle. Recent results obtained with specific SRF knock-out models, using the Cre-LopP system, emphasize a crucial role for SRF in postnatal skeletal muscle growth and regeneration possibly due to the direct binding of Interleukin-4 (IL-4) and Insulin-like growth factor (IGF-I) promoters in vivo. SRF also enhances the hypertrophic process in muscle fibers after mechnical overloading. During muscle hypertrophy, SRF seems to promote the proliferation and differentiation of muscle stem satellite cells after the activation of upstream mediators (STARS, MRTF-A, and RhoA). Our recent study has demonstrated a marked decrease in the amounts of SRF, STARS, and MRTF-A in sarcopenic muscles of mice. A decrease of SRF expression achieved using a transgenic approach was found to accelerate the atrophic process in muscle fibers and result in the significant deposition of intermuscle lipid with aging. A number of experimental models and human disorders are associated with changes in SRF expression, suggesting that SRF has a role in the pathogenesis of disease. This review summarizes the functional role of SRF and SRF-linked molecules during myogenesis, postnatal growth, hypertrophy, regeneration, and muscle wasting (ex. sarcopenia). Controlling the amount of SRF may be effective in the treatment of muscular disorders. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Frontiers in Pathology and Genetics Science and Engineering Publishing Company

Serum Response Factor (SRF)-Dependent Signaling in Regenerating, Hypertrophied, and Pahological Skeletal Muscle

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Publisher
Science and Engineering Publishing Company
Copyright
Science and Engineering Publishing Company
ISSN
2330-1805
eISSN
2330-1813

Abstract

Serum response factor (SRF) is an ubiquitously expressed member of the MADS (MCM1, Agamous, Deficiens, SRF) box transcription factor family, sharing a highly conserved DNA-binding/dimerization domain, which binds the core sequence of SRE/CArG boxes (CC (A/T)6 GG). In addition, SRF is as well a widely expressed transcription factor involved in orchestrating disparate programs of gene expression linked to differentiation and cellular growth in smooth, cardiac, and skeletal muscle. Recent results obtained with specific SRF knock-out models, using the Cre-LopP system, emphasize a crucial role for SRF in postnatal skeletal muscle growth and regeneration possibly due to the direct binding of Interleukin-4 (IL-4) and Insulin-like growth factor (IGF-I) promoters in vivo. SRF also enhances the hypertrophic process in muscle fibers after mechnical overloading. During muscle hypertrophy, SRF seems to promote the proliferation and differentiation of muscle stem satellite cells after the activation of upstream mediators (STARS, MRTF-A, and RhoA). Our recent study has demonstrated a marked decrease in the amounts of SRF, STARS, and MRTF-A in sarcopenic muscles of mice. A decrease of SRF expression achieved using a transgenic approach was found to accelerate the atrophic process in muscle fibers and result in the significant deposition of intermuscle lipid with aging. A number of experimental models and human disorders are associated with changes in SRF expression, suggesting that SRF has a role in the pathogenesis of disease. This review summarizes the functional role of SRF and SRF-linked molecules during myogenesis, postnatal growth, hypertrophy, regeneration, and muscle wasting (ex. sarcopenia). Controlling the amount of SRF may be effective in the treatment of muscular disorders.

Journal

Frontiers in Pathology and Genetics – Science and Engineering Publishing Company

Published: Jun 1, 2013

Keywords: Skeletal Muscle, Serum Response Factor, Myod, Hypertrophy, Regeneration

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