KLF15 Is an Essential Negative Regulatory Factor for the Cardiac Remodeling Response to Pressure Overload
KLF15 Is an Essential Negative Regulatory Factor for the Cardiac Remodeling Response to Pressure Overload
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DOI：
10.1159/000369382
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发表时间：
2015-01-01
期刊：
影响因子：
1.9
通讯作者：
Chen, Lin
中科院分区：
文献类型：
--
作者：
Yu, Yang;Ma, Jie;Chen, Lin
目的：探讨克虏伯样因子15（KLF15）在心脏重构和间质纤维化中的作用机制。方法:采用体内主动脉缩窄、一段时间卸压的方法建立大鼠模型,测定心功能、心肌病理变化以及KLF15、转化生长因子-β(TGF-β)、结缔组织生长因子(CTGF)、心肌素相关转录因子A(MRTF-A)的表达水平。此外，体外培养心脏成纤维细胞，并用KLF15-shRNA或KLF15重组腺病毒处理，建立TGF-β介导的心脏成纤维细胞肥大模型，并分析细胞形态、胶原分泌和4种细胞因子表达水平的变化。结果：体内压力超负荷损害心脏功能并导致心肌肥厚和纤维化。这些变化伴随着 KLF15 mRNA 水平的下调和其他因子表达的增加。卸载时的反应则相反。在体外细胞实验中，通过特异性靶向KLF15基因，观察到4种细胞因子表达水平以及I型和III型胶原蛋白含量的变化。结论：在机械或代谢因素诱导的心肌重塑过程中，KLF15调节TGF-β、CTGF、MRTF-A的表达，可以改善甚至逆转心肌纤维化，改善心功能。 (C) 2015 S. Karger AG，巴塞尔
Objective:To investigate the mechanism of Kruppel-like factor 15 (KLF15) in cardiac remodeling and interstitial fibrosis. Methods: A rat model was established by in vivo aortic coarctation followed by a period of pressure unloading and used to measure heart function, myocardial pathological changes, and KLF15, transforming growth factor-beta (TGF-beta), connective tissue growth factor (CTGF), and myocardin-related transcription factor A (MRTF-A) expression levels. In addition, cardiac fibroblasts were cultured in vitro and treated with KLF15-shRNA or KLF15 recombinant adenovirus to establish a TGF-beta-mediated cardiac fibroblast hypertrophy model and analyze cell morphology, collagen secretion, and changes in the expression levels of 4 cytokines. Results: In vivo pressure overload impaired cardiac function and resulted in myocardial hypertrophy and fibrosis. These changes were accompanied by the downregulation of KLF15 mRNA levels and increased expression of the other factors. The response to unloading was the opposite. In in vitro cell experiments, by specifically targeting the KLF15 gene, changes in the expression levels of the 4 cytokines and the amounts of collagen I and III were observed. Conclusions: In myocardial remodeling processes induced by mechanical or metabolic factors, KLF15 regulates TGF-beta, CTGF, and MRTF-A expression and can ameliorate or even reverse myocardial fibrosis and improve cardiac function. (C) 2015 S. Karger AG, Basel