Angiotensin II-induced cardiac hypertrophy and fibrosis are promoted in mice lacking Fgf16.
Angiotensin II-induced cardiac hypertrophy and fibrosis are promoted in mice lacking Fgf16.
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DOI：
10.1111/gtc.12055
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发表时间：
2013-07
期刊：
影响因子：
--
通讯作者：
Itoh N
中科院分区：
文献类型：
--
作者：
Matsumoto E;Sasaki S;Kinoshita H;Kito T;Ohta H;Konishi M;Kuwahara K;Nakao K;Itoh N
成纤维细胞生长因子（Fgfs）是参与发育、修复和代谢的多效蛋白。Fgf16主要在心脏表达。然而，由于Fgf16基因敲除小鼠的心脏功能基本正常，其作用尚不清楚。为了阐明Fgf16在心脏中的病理生理作用，我们在Fgf16基因敲除小鼠中检测了血管紧张素ii诱导的心脏肥大和纤维化。通过增强Tgf-β1在Fgf16基因敲除小鼠中的表达，可显著促进血管紧张素ii诱导的心肌肥大和纤维化。出乎意料的是，对心脏重塑的反应与Fgf2敲除小鼠明显相反。这些结果表明Fgf16可能阻止心脏重塑，尽管Fgf2促进心脏重塑。血管紧张素II诱导Fgf2表达后，诱导心肌Fgf16表达。在培养的心肌细胞中，Fgf2可促进Fgf16的表达。此外，Fgf16可拮抗fgf2诱导的Tgf-β1在培养的心肌细胞和非心肌细胞中的表达。这些结果提示了Fgf16通过拮抗Fgf2预防血管紧张素ii诱导的心脏肥大和纤维化的可能机制。本研究结果将为Fgf信号在心脏重构中的作用提供新的见解。
Fibroblast growth factors (Fgfs) are pleiotropic proteins involved in development, repair and metabolism. Fgf16 is predominantly expressed in the heart. However, as the heart function is essentially normal in Fgf16 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 Fgf16 knockout mice. Angiotensin II-induced cardiac hypertrophy and fibrosis were significantly promoted by enhancing Tgf-β1 expression in Fgf16 knockout mice. Unexpectedly, the response to cardiac remodeling was apparently opposite to that in Fgf2 knockout mice. These results indicate that Fgf16 probably prevents cardiac remodeling, although Fgf2 promotes it. Cardiac Fgf16 expression was induced after the induction of Fgf2 expression by angiotensin II. In cultured cardiomyocytes, Fgf16 expression was promoted by Fgf2. In addition, Fgf16 antagonized Fgf2-induced Tgf-β1 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.
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