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

17 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

Fingerprint

Myostatin
Cardiac Myocytes
Muscle
Follistatin
Skeletal Muscle
Stem Cells
Cell proliferation
Growth Differentiation Factors
Stem cells
Cell Proliferation
Mammals
Cyclin D1
Cells
Growth
Cell Cycle
Down-Regulation
Muscles

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Skeletal muscle-derived progenitors capable of differentiating into cardiomyocytes proliferate through myostatin-independent TGF-β family signaling. / Nomura, Tetsuya; Ueyama, Tomomi; Ashihara, Eishi; Tateishi, Kento; Asada, Satoshi; Nakajima, Norio; Isodono, Koji; Takahashi, Tomosaburo; Matsubara, Hiroaki; Oh, Hidemasa.

In: Biochemical and Biophysical Research Communications, Vol. 365, No. 4, 25.01.2008, p. 863-869.

Research output: Contribution to journalArticle

Nomura, Tetsuya ; Ueyama, Tomomi ; Ashihara, Eishi ; Tateishi, Kento ; Asada, Satoshi ; Nakajima, Norio ; Isodono, Koji ; Takahashi, Tomosaburo ; Matsubara, Hiroaki ; Oh, Hidemasa. / Skeletal muscle-derived progenitors capable of differentiating into cardiomyocytes proliferate through myostatin-independent TGF-β family signaling. In: Biochemical and Biophysical Research Communications. 2008 ; Vol. 365, No. 4. pp. 863-869.
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