Smooth muscle cells and myofibroblasts use distinct transcriptional mechanisms for smooth muscle α-actin expression

Qiong Gan, Tadashi Yoshida, Jian Li, Gary K. Owens

Research output: Contribution to journalArticle

65 Citations (Scopus)

Abstract

There has been considerable controversy regarding the lineage relationship between smooth muscle cells (SMCs) and myofibroblasts, because they express a number of common cell-selective markers including smooth muscle (SM) α-actin. We have shown previously that MCAT elements within the SM α-actin promoter confer differential activity in cultured SMCs versus myofibroblasts. In the present study, to determine the role of MCAT elements in vivo, we generated transgenic mice harboring an SM α-actin promoter-enhancer-LacZ reporter gene containing MCAT element mutations and compared transgene expression patterns with wild-type SM α-actin promoter-enhancer-LacZ transgenic mice. Results showed no differences in LacZ expression patterns in adult SMC-containing tissues. However, of interest, mutations of MCAT elements selectively abolished transgene expression in myofibroblasts within granulation tissue of skin wounds. In addition, mutations of MCAT elements caused a delay in the induction of transgene expression in SMCs, as well as loss of expression in cardiac and skeletal muscles during embryogenesis. Results of small interfering RNA-induced knockdown experiments showed that RTEF-1 regulated SM α-actin transcription in myofibroblasts, but not in differentiated SMCs. Moreover, quantitative chromatin immunoprecipitation assays revealed that RTEF-1 bound to the MCAT element-containing region within the SM α-actin promoter in myofibroblasts, whereas transcriptional enhancer factor (TEF)-1 was bound to the same region in differentiated SMCs. These results provide novel evidence that, although both SMCs and myofibroblasts express SM α-actin, they use distinct transcriptional control mechanisms for regulating its expression. Results also indicate that the MCAT element-mutated SM α-actin promoter-enhancer is a useful tool to direct gene expression selectively in differentiated SMCs.

Original languageEnglish
Pages (from-to)883-892
Number of pages10
JournalCirculation research
Volume101
Issue number9
DOIs
Publication statusPublished - 2007 Oct 1
Externally publishedYes

Keywords

  • MCAT elements
  • Smooth muscle α-actin
  • Transcriptional enhancer factor-1
  • Transgenic mouse

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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