title: Fn14 is regulated via the RhoA pathway and mediates nuclear factor-kappaB activation by Angiotensin II.
abstract: 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 inin vivomodel. We therefore assess the expression and regulation of Fn14 in cardiomyocytes andin vivomodels induced by Ang II. In order to study the regulation of Fn14, cardiac remodeling was established in rats and neonatal cardiomyocytes were used inin vitromodel. As well, Ang II is able to strongly induce Fn14 expression inin vivoandin vitromodels. 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 inin vivoandin vitromodels 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.
authors.affiliation: Department of Cardiology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University No. 3 East Qingchun Road, Hangzhou 310016, Zhejiang Province, PR China.
authors.forename: Zhengwei
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Cardiology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University No. 3 East Qingchun Road, Hangzhou 310016, Zhejiang Province, PR China.
authors.forename: Zhida
authors.initials: Z
authors.lastname: Shen
authors.affiliation: Department of Cardiology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University No. 3 East Qingchun Road, Hangzhou 310016, Zhejiang Province, PR China.
authors.forename: Lailing
authors.initials: L
authors.lastname: Du
authors.affiliation: Department of Cardiology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University No. 3 East Qingchun Road, Hangzhou 310016, Zhejiang Province, PR China.
authors.forename: Jialin
authors.initials: J
authors.lastname: He
authors.affiliation: Department of Cardiology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University No. 3 East Qingchun Road, Hangzhou 310016, Zhejiang Province, PR China.
authors.forename: Shengyu
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Cardiology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University No. 3 East Qingchun Road, Hangzhou 310016, Zhejiang Province, PR China.
authors.forename: Jiefang
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University No. 3 East Qingchun Road, Hangzhou 310016, Zhejiang Province, PR China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Luan
authors.affiliation: Department of Cardiology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University No. 3 East Qingchun Road, Hangzhou 310016, Zhejiang Province, PR China.
authors.forename: Guosheng
authors.initials: G
authors.lastname: Fu
keywords: Ang II; Fn14; NF-κB; RhoA