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.