Angiotensin II‐induced cardiac hypertrophy and fibrosis are promoted in mice lacking Fgf16. (18th April 2013)

• Record Type: Journal Article
• Authors: Matsumoto, Emi; Sasaki, Sayaka; Kinoshita, Hideyuki; Kito, Takuya; Ohta, Hiroya; Konishi, Morichika; Kuwahara, Koichiro; Nakao, Kazuwa; Itoh, Nobuyuki
• Is Part Of: Genes to cells. Volume 18:Number 7(2013:Jul.)
• Page Start: 544
• Page End: 553
• Publication Date: 2013-04-18
• Subjects: Cytogenetics -- Periodicals; Cells -- Mechanical properties -- Periodicals; Molecular genetics -- Periodicals; Genes -- Periodicals; Molecular biology -- Periodicals; Cytology -- Periodicals; Biomechanics -- Periodicals; 571.6
• DOI: 10.1111/gtc.12055
• Languages: English
• ISSNs: 1356-9597

Abstract

<abstract abstract-type="main" id="gtc12055-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Fibroblast growth factors (Fgfs) are pleiotropic proteins involved in development, repair and metabolism. <italic>Fgf16</italic> is predominantly expressed in the heart. However, as the heart function is essentially normal in <italic>Fgf16</italic> knockout mice, its role has remained unclear. To elucidate the pathophysiological role of Fgf16 in the heart, we examined angiotensin II‐induced cardiac hypertrophy and fibrosis in <italic>Fgf16</italic> knockout mice. Angiotensin II‐induced cardiac hypertrophy and fibrosis were significantly promoted by enhancing <italic>Tgf‐β</italic><sub><italic>1</italic></sub> expression in <italic>Fgf16</italic> knockout mice. Unexpectedly, the response to cardiac remodeling was apparently opposite to that in <italic>Fgf2</italic> knockout mice. These results indicate that Fgf16 probably prevents cardiac remodeling, although Fgf2 promotes it. Cardiac <italic>Fgf16</italic> expression was induced after the induction of <italic>Fgf2</italic> expression by angiotensin II. In cultured cardiomyocytes, <italic>Fgf16</italic> expression was promoted by Fgf2. In addition, Fgf16 antagonized Fgf2‐induced <italic>Tgf‐β</italic><sub><italic>1</italic></sub> expression in cultured cardiomyocytes and noncardiomyocytes. These results suggest a possible mechanism whereby Fgf16 prevents angiotensin II‐induced cardiac hypertrophy and fibrosis by antagonizing Fgf2. The present findings should provide new insights into the roles of Fgf signaling in cardiac remodeling.</p> </abstract>