Myocardin and Prx1 Contribute to Angiotensin II-Induced Expression of Smooth Muscle α-Actin

Tadashi Yoshida, Mark H. Hoofnagle, Gary K. Owens

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

Previous studies demonstrated that angiotensin II (Ang II)-induced hypertrophy of smooth muscle cells (SMCs) was associated with increased transcription of SM α-actin gene. The aim of the present study was to determine whether myocardin, a SMC-selective cofactor of serum response factor (SRF), contributed to Ang II-induced increases in SM α-actin transcription. Results showed that Ang II increased myocardin mRNA expression as well as SM α-actin mRNA expression via the Ang II type 1 receptor in cultured rat aortic SMCs. Cotransfection studies revealed that CArG elements were required for Ang II-induced transcription of SM α-actin gene, and a dominant-negative form of myocardin or a short interfering RNA (siRNA) specific for myocardin decreased Ang II-induced SM α-actin transcription. Prx1, a homeodomain protein whose expression was increased by Ang II, also increased SM α-actin gene transcription in part via CArG elements, and siRNA specific for Prx1 markedly decreased basal and Ang II-induced SM α-actin transcription. Electrophoretic mobility shift assay showed that myocardin and Ang II, respectively, increased formation of a SMC-specific CArG-SRF-myocardin higher order complex. However, Ang II had no effect on binding between myocardin and SRF as determined by a mammalian two-hybrid assay, suggesting that Ang II-induced increases in formation of CArG-SRF-myocardin complex was the result of increased SRF binding to CArG elements and increased myocardin expression. Taken together, these results support a model in which Ang II-induced increases in expression of SM α-actin are mediated through Prx1-dependent increases in SRF binding to CArG elements and subsequent recruitment of myocardin.

Original languageEnglish
Pages (from-to)1075-1082
Number of pages8
JournalCirculation research
Volume94
Issue number8
DOIs
Publication statusPublished - 2004 Apr 30
Externally publishedYes

Keywords

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

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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