Forced expression of myocardin is not sufficient for induction of smooth muscle differentiation in multipotential embryonic cells

Tadashi Yoshida, Keiko Kawai-Kowase, Gary K. Owens

Research output: Contribution to journalArticle

79 Citations (Scopus)

Abstract

Objective-Myocardin, a coactivator of serum response factor, has been shown to be required for expression of multiple CArG-dependent smooth muscle cell (SMC) marker genes. The aim of the present study was to determine whether myocardin alone is sufficient to induce SMC lineage in multipotential stem cells as evidenced by activation of the entire SMC differentiation program. Methods and Results-Overexpression of myocardin induced only a subset of SMC marker genes, including smooth muscle (SM) α-actin, SM-myosin heavy chain (MHC), SM22α, calponin, and desmin in A404 SMC precursor cells, whereas expression of smoothelin-B, aortic carboxypeptidase-like protein, and focal adhesion kinase-related nonkinase, whose promoters lack efficacious CArG elements, was not induced. Similar results were obtained in cultured SMCs, 10T1/2 cells, and embryonic stem cells. Moreover, myocardin inappropriately induced expression of skeletal and cardiac CArG-dependent genes in cultured SMCs. Stable overexpression of dominant-negative myocardin in A404 cells resulted in impaired induction of SM α-actin and SM-MHC by all trans-retinoic acid but had no effect on induction of smoothelin-B and aortic carboxypeptidase-like protein expression. Conclusions-Taken together with previous studies, results demonstrate that myocardin is required for the induction of CArG-dependent SMC marker genes but is not sufficient to initiate the complete SMC differentiation program.

Original languageEnglish
Pages (from-to)1596-1601
Number of pages6
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume24
Issue number9
DOIs
Publication statusPublished - 2004 Sep 1
Externally publishedYes

Keywords

  • CArG element
  • Serum response factor
  • Smooth muscle cells
  • Transcriptional coactivator

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Fingerprint Dive into the research topics of 'Forced expression of myocardin is not sufficient for induction of smooth muscle differentiation in multipotential embryonic cells'. Together they form a unique fingerprint.

  • Cite this