Yu Yang, Ma Jie, Xiao Yingbin, Yang Qingjun, Kang Huali, Zhen Jie, Yu Lang, Chen Lin
Division of Cardiac Surgery, Xinqiao Hospital Affiliated to the Third Military Medical University, Chongqing, PR China.
Cardiology. 2015;130(3):143-52. doi: 10.1159/000369382. Epub 2015 Jan 24.
To investigate the mechanism of Krüppel-like factor 15 (KLF15) in cardiac remodeling and interstitial fibrosis.
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-β (TGF-β), 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-β-mediated cardiac fibroblast hypertrophy model and analyze cell morphology, collagen secretion, and changes in the expression levels of 4 cytokines.
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.
In myocardial remodeling processes induced by mechanical or metabolic factors, KLF15 regulates TGF-β, CTGF, and MRTF-A expression and can ameliorate or even reverse myocardial fibrosis and improve cardiac function.
探讨Krüppel样因子15（KLF15）在心脏重塑和间质纤维化中的作用机制。
通过体内主动脉缩窄建立大鼠模型，随后进行一段时间的压力卸载，用于测量心脏功能、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）和心肌相关转录因子A（MRTF-A）的表达水平。此外，体外培养心脏成纤维细胞，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，分析细胞形态、胶原蛋白分泌以及4种细胞因子表达水平的变化。
体内压力过载损害心脏功能，导致心肌肥大和纤维化。这些变化伴随着KLF15 mRNA水平的下调以及其他因子表达的增加。卸载后的反应则相反。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型胶原蛋白量的变化。
在由机械或代谢因素诱导的心肌重塑过程中，KLF15调节TGF-β、CTGF和MRTF-A的表达，并可改善甚至逆转心肌纤维化，改善心脏功能。
