title: Krüppel-like factor 4 transcriptionally regulates TGF-β1 and contributes to cardiac myofibroblast differentiation.
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.
authors: Beijing Anzhen Hospital, Capital Medical University, The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing, China.
authors: Yi
authors: Y
authors: Zhang
authors: Ying
authors: Y
authors: Wang
authors: Yan
authors: Y
authors: Liu
authors: Nanping
authors: N
authors: Wang
authors: Yongfen
authors: Y
authors: Qi
authors: Jie
authors: J
authors: Du
mesh_terms: D000804:Angiotensin II / Q000008:administration & dosage; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics*; D003094:Collagen / Q000096:biosynthesis; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D032386:Myoblasts, Cardiac / Q000166:cytology* / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism; D058628:Myofibroblasts / Q000166:cytology* / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D015533:Transcriptional Activation; D053773:Transforming Growth Factor beta1 / Q000235:genetics* / Q000378:metabolism
chemical_list: C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D053773:Transforming Growth Factor beta1; D000804:Angiotensin II; D003094:Collagen
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