Li Zhengwei, Shen Zhida, Du Lailing, He Jialin, Chen Shengyu, Zhang Jiefang, Luan Yi, Fu Guosheng
Department of Cardiology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University No. 3 East Qingchun Road, Hangzhou 310016, Zhejiang Province, PR China.
Am J Transl Res. 2016 Dec 15;8(12):5386-5398. eCollection 2016.
Angiotesin II (Ang II) plays an important role in cardiac remodeling. Fibroblast growth factor inducible-14 (Fn14) is the smallest member of the tumor necrosis factor superfamily of receptors. Currently, little is known about the functional role of Fn14 in the heart. Chiefly, we observe the up-regulation of extracellular matrix in model. We therefore assess the expression and regulation of Fn14 in cardiomyocytes and models induced by Ang II. In order to study the regulation of Fn14, cardiac remodeling was established in rats and neonatal cardiomyocytes were used in model. As well, Ang II is able to strongly induce Fn14 expression in and models. Fn14 is mediated via RhoA pathways, since siRNA against RhoA prevented the expression of Fn14 in cardiomyocytes. Pretreatment of cardiomyoctes with siRNA against NF-κB and IκBα also decreased Fn14 expression induced by Ang II. We here describe for the first time Ang II regulation of Fn14 in and models via RhoA, NF-κB and NF-κB driven gene signaling pathway. In conclusion, Fn14 may be important in regulating the process of cardiac remodeling induced by Ang II.
血管紧张素II（Ang II）在心脏重塑中起重要作用。成纤维细胞生长因子诱导14（Fn14）是肿瘤坏死因子受体超家族中最小的成员。目前，关于Fn14在心脏中的功能作用知之甚少。主要地，我们在模型中观察到细胞外基质的上调。因此，我们评估了Fn14在心肌细胞以及由Ang II诱导的模型中的表达和调控。为了研究Fn14的调控，在大鼠中建立了心脏重塑模型，并在模型中使用新生心肌细胞。同样，Ang II能够在细胞和模型中强烈诱导Fn14表达。Fn14是通过RhoA途径介导的，因为针对RhoA的小干扰RNA（siRNA）可阻止心肌细胞中Fn14的表达。用针对NF-κB和IκBα的siRNA预处理心肌细胞也可降低Ang II诱导的Fn14表达。我们首次在此描述了在细胞和模型中Ang II通过RhoA、NF-κB和NF-κB驱动的基因信号通路对Fn14的调控。总之，Fn14在调节由Ang II诱导的心脏重塑过程中可能很重要。
