Fn14 is regulated via the RhoA pathway and mediates nuclear factor-kappaB activation by Angiotensin II

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 in vivo model. We therefore assess the expression and regulation of Fn14 in cardiomyocytes and in vivo 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 in vitro model. As well, Ang II is able to strongly induce Fn14 expression in in vivo and in vitro 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 in vivo and in vitro 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.