FGF13 Is a Novel Regulator of NF-κB and Potentiates Pathological Cardiac Hypertrophy

Overview

Journal iScience

Publisher Cell Press

Date 2020 Oct 22

PMID 33089113

Citations 14

Authors

Jia Sun

Chao Niu

Weijian Ye

Ning An

Gen Chen

Xiaozhong Huang

Jianan Wang

Xixi Chen

Yingjie Shen

Shuai Huang

Ying Wang

Xu Wang

Yang Wang

Litai Jin

Weitao Cong

Xiaokun Li

Affiliations

Soon will be listed here.

Abstract

FGF13 is an intracellular FGF factor. Its role in cardiomyopathies has been rarely investigated. We revealed that endogenous FGF13 is up-regulated in cardiac hypertrophy accompanied by increased nuclear localization. The upregulation of FGF13 plays a deteriorating role both in hypertrophic cardiomyocytes and mouse hearts. Mechanistically, FGF13 directly interacts with p65 by its nuclear localization sequence and co-localizes with p65 in the nucleus in cardiac hypertrophy. FGF13 deficiency inhibits NF-κB activation in ISO-treated NRCMs and TAC-surgery mouse hearts, whereas FGF13 overexpression shows the opposite trend. Moreover, FGF13 overexpression alone is sufficient to activate NF-κB in cardiomyocytes. The interaction between FGF13 and p65 or the effects of FGF13 on NF-κB have nothing to do with IκB. Together, an IκB-independent mechanism for NF-κB regulation has been revealed in cardiomyocytes both under basal and stressful conditions, suggesting the promising application of FGF13 as a therapeutic target for pathological cardiac hypertrophy and heart failure.

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