Skeletal muscle-derived progenitors capable of differentiating into cardiomyocytes proliferate through myostatin-independent TGF-β family signaling

Tetsuya Nomura, Tomomi Ueyama, Eishi Ashihara, Kento Tateishi, Satoshi Asada, Norio Nakajima, Koji Isodono, Tomosaburo Takahashi, Hiroaki Matsubara, Hidemasa Oh

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

The existence of skeletal muscle-derived stem cells (MDSCs) has been suggested in mammals; however, the signaling pathways controlling MDSC proliferation remain largely unknown. Here we report the isolation of myosphere-derived progenitor cells (MDPCs) that can give rise to beating cardiomyocytes from adult skeletal muscle. We identified that follistatin, an antagonist of TGF-β family members, was predominantly expressed in MDPCs, whereas myostatin was mainly expressed in myogenic cells and mature skeletal muscle. Although follistatin enhanced the replicative growth of MDPCs through Smad2/3 inactivation and cell cycle progression, disruption of myostatin did not increase the MDPC proliferation. By contrast, inhibition of activin A (ActA) or growth differentiation factor 11 (GDF11) signaling dramatically increased MDPC proliferation via down-regulation of p21 and increases in the levels of cdk2/4 and cyclin D1. Thus, follistatin may be an effective progenitor-enhancing agent neutralizing ActA and GDF11 signaling to regulate the growth of MDPCs in skeletal muscle.

Original languageEnglish
Pages (from-to)863-869
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume365
Issue number4
DOIs
Publication statusPublished - Jan 25 2008
Externally publishedYes

Keywords

  • Follistatin
  • Muscle progenitor cells
  • Myostatin
  • Proliferation
  • TGF-β

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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