Semaphorin 3A promotes activation of Pax7, Myf5, and MyoD through inhibition of emerin expression in activated satellite cells

Mulan Qahar, Yuko Takuma, Wataru Mizunoya, Ryuichi Tatsumi, Yoshihide Ikeuchi, Mako Nakamura

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

We previously showed that Semaphorin 3A (Sema3A) expression was induced when quiescent muscle satellite cells were stimulated by hepatocyte growth factor and became activated satellite cells (ASCs). However, how Sema3A regulates genes in the early phase of ASCs remains unclear. In this study, we investigated whether Sema3A signaling can regulate the early phase of ASCs, an important satellite cell stage for postnatal growth, repair, and maintenance of skeletal muscle. We showed that expression of the myogenic proliferation regulatory factors Pax7 and Myf5 was decreased in myoblasts transfected with Sema3A siRNA. These cells failed to activate expression MyoD, another myogenic proliferation regulatory factor, during differentiation. Interestingly, some of the Sema3A-depleted cells did not express Pax7 and MyoD and had enlarged nuclei and very large cytoplasmic areas. We also observed that Pax7 and Myf5 expression was increased in Myc-Sema3A overexpressing myoblasts. BrdU analysis indicated that Sema3A regulated proliferation of ASCs. These findings suggest that Sema3A signaling can modulate expression of Pax7, Myf5, and MyoD. Moreover, we found that expression of emerin, an inner nuclear membrane protein, was regulated by Sema3A signaling. Emerin was identified by positional cloning as the gene responsible for the X-linked form of Emery-Dreifuss muscular dystrophy (X-EDMD). In conclusion, our results support a role for Sema3A in maintaining ASCs through regulation, via emerin, of Pax7, Myf5, and MyoD expression.

Original languageEnglish
Pages (from-to)529-539
Number of pages11
JournalFEBS Open Bio
Volume6
Issue number6
DOIs
Publication statusPublished - Jun 1 2016

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

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