Transforming growth factor-β1-induced transcript 1 protein, a novel marker for smooth muscle contractile phenotype, is regulated by serum response factor/myocardin protein

Xiaobo Wang, Guoqing Hu, Courtney Betts, Erin Yund Harmon, Rebecca S. Keller, Livingston Van De Water, Jiliang Zhou

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Serum response factor (SRF) plays a central role in regulating expression of smooth muscle-specific genes partly by associating with the potent tissue-specific cofactor myocardin. Previous studies have shown that transforming growth factor-β1-induced transcript 1 (TGFB1I1, also known as Hic-5) is a TGF-β- responsive gene and is involved in the cellular response to vascular injury, but the regulation of TGFB1I1 expression remains elusive. In this report, we demonstrated that TGFB1I1 is a novel marker for the smooth muscle contractile phenotype and is regulated by SRF/myocardin. We found that TGFB1I1 is specifically expressed in smooth muscle cells (SMCs) and in smooth muscle-rich tissues. Furthermore, TGFB1I1 expression is significantly down-regulated in a variety of models for smooth muscle phenotypic modulation. The TGFB1I1 promoter contains an evolutionarily conserved CArG element, and this element is indispensible for myocardin-induced transactivation of TGFB1I1 promoter. By oligonucleotide pulldown and chromatin immunoprecipitation assays, we found that SRF binds to this CArG element in vitro and in vivo. Ectopic expression of myocardin is sufficient to induce endogenous TGFB1I1 expression in multiple cell lines whereas knockingdown myocardin or SRF significantly attenuated TGFB1I1 expression in SMCs. Furthermore, our data demonstrated that SRF is essential for TGF-β-mediated induction of TGFB1I1. Finally, silencing of TGFB1I1 expression significantly promotes SMC proliferation. Collectively, this study provides the first evidence that TGFB1I1 is not only an SRF/myocardin-regulated smooth muscle marker but also critical for maintaining smooth muscle contractile phenotype by inhibiting smooth muscle proliferation.

Original languageEnglish (US)
Pages (from-to)41589-41599
Number of pages11
JournalJournal of Biological Chemistry
Volume286
Issue number48
DOIs
StatePublished - Dec 2 2011

Fingerprint

Serum Response Factor
Transforming Growth Factors
Smooth Muscle
Muscle
Phenotype
Proteins
Smooth Muscle Myocytes
Chromatin Immunoprecipitation
Vascular System Injuries
Genes
Cells
myocardin
Tissue
Oligonucleotides
Transcriptional Activation
Cell proliferation
Cell Proliferation
Cell Line
Chromatin
Muscles

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Transforming growth factor-β1-induced transcript 1 protein, a novel marker for smooth muscle contractile phenotype, is regulated by serum response factor/myocardin protein. / Wang, Xiaobo; Hu, Guoqing; Betts, Courtney; Harmon, Erin Yund; Keller, Rebecca S.; Van De Water, Livingston; Zhou, Jiliang.

In: Journal of Biological Chemistry, Vol. 286, No. 48, 02.12.2011, p. 41589-41599.

Research output: Contribution to journalArticle

Wang, Xiaobo ; Hu, Guoqing ; Betts, Courtney ; Harmon, Erin Yund ; Keller, Rebecca S. ; Van De Water, Livingston ; Zhou, Jiliang. / Transforming growth factor-β1-induced transcript 1 protein, a novel marker for smooth muscle contractile phenotype, is regulated by serum response factor/myocardin protein. In: Journal of Biological Chemistry. 2011 ; Vol. 286, No. 48. pp. 41589-41599.
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