我重点实验室博士生张祎于近日在PLoS One 发表文章Kruppel-Like Factor 4 Transcriptionally Regulates TGF-β1 and Contributes to Cardiac Myofibroblast Differentiation。文章探讨了在心脏成纤维细胞内，血管紧张素II刺激导致核转录因子Klf4活化后，诱导肌成纤维细胞分化和胶原合成的生物学效应;采用ChiP Seq等方法验证了Klf4能通过转录调控包括TGF-β1在内的多种纤维化相关基因表达，发挥其生物学效应。这一结果揭示了Klf4在高血压导致心脏纤维化病理过程中的作用，并为进一步研究核转录因子与高血压靶器官损害提供了线索。

文章英文摘要：

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-b1 expression, as well as its contribution to cardiac fibrosis, is unknown. We studied the role of Kruppel-like family transcription factors in Ang II-induced myofibroblast formation. We found that among the Kruppel-like family members, Kruppel-like factor 4 (Klf4) was the highest expressed form in isolated cardiac fibroblasts after Ang II treatment. Klf4 increased expression of a-SMA and collagen, as well as increased myofibroblast formation. ChIP assays showed that Klf4 specifically bound to the TGF-b1 promoter. Deletion and mutagenesis analysis showed that the sites at -184~- 180 bp and -45~-41 bp in the TGF-β1 promoter were responsiblefor Klf4 transactivation of the TGF-β1 promoter. Our studies demonstrate that Klf4 plays a pivotal role in Ang II-inducedcardiac myofibroblast differentiation and collagen synthesis through transcriptional upregulation of TGF-β1.