Angiotensin II ‐induced cardiac hypertrophy and fibrosis are promoted in mice lacking F gf16

Fibroblast growth factors ( F gfs) are pleiotropic proteins involved in development, repair and metabolism. F gf16 is predominantly expressed in the heart. However, as the heart function is essentially normal in F gf16 knockout mice, its role has remained unclear. To elucidate the pathophysiological role of F gf16 in the heart, we examined angiotensin II ‐induced cardiac hypertrophy and fibrosis in F gf16 knockout mice. Angiotensin II ‐induced cardiac hypertrophy and fibrosis were significantly promoted by enhancing T gf‐β 1 expression in F gf16 knockout mice. Unexpectedly, the response to cardiac remodeling was apparently opposite to that in F gf2 knockout mice. These results indicate that F gf16 probably prevents cardiac remodeling, although F gf2 promotes it. Cardiac F gf16 expression was induced after the induction of F gf2 expression by angiotensin II . In cultured cardiomyocytes, F gf16 expression was promoted by F gf2. In addition, F gf16 antagonized F gf2‐induced T gf‐β 1 expression in cultured cardiomyocytes and noncardiomyocytes. These results suggest a possible mechanism whereby F gf16 prevents angiotensin II ‐induced cardiac hypertrophy and fibrosis by antagonizing F gf2. The present findings should provide new insights into the roles of F gf signaling in cardiac remodeling.