Krüppel-Like Factor 4 Transcriptionally Regulates TGF-β1 and Contributes to Cardiac Myofibroblast Differentiation

Yi Zhang, Ying Wang, Yan Liu, Nanping Wang, Yongfen Qi, Jie Du

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

Angiotensin II (Ang II) plays a major role in the pathogenesis of cardiac fibrosis in hypertension. It is known that Ang II induces TGF-β1 expression. How transcription mediates Ang II-induced TGF-β1 expression, as well as its contribution to cardiac fibrosis, is unknown. We studied the role of Krüppel-like family transcription factors in Ang II-induced myofibroblast formation. We found that among the Krüppel-like family members, Krüppel-like factor 4 (Klf4) was the highest expressed form in isolated cardiac fibroblasts after Ang II treatment. Klf4 increased expression of α-SMA and collagen, as well as increased myofibroblast formation. ChIP assays showed that Klf4 specifically bound to the TGF-β1 promoter. Deletion and mutagenesis analysis showed that the sites at -184∼-180 bp and -45∼-41 bp in the TGF-β1 promoter were responsible for Klf4 transactivation of the TGF-β1 promoter. Our studies demonstrate that Klf4 plays a pivotal role in Ang II-induced cardiac myofibroblast differentiation and collagen synthesis through transcriptional upregulation of TGF-β1.

Original languageEnglish (US)
Article numbere63424
JournalPloS one
Volume8
Issue number4
DOIs
StatePublished - Apr 30 2013

ASJC Scopus subject areas

  • General

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