Endocrine Protection of Ischemic Myocardium by FGF21 from the Liver and Adipose Tissue

被引：152

作者：

Liu, Shu Q. ^{[1
]}

Roberts, Derek ^{[1
]}

Kharitonenkov, Alexei ^{[2
]}

Zhang, Brian ^{[1
]}

Hanson, Samuel M. ^{[1
]}

Li, Yan Chun ^{[3
]}

Zhang, Li-Qun ^{[4
]}

Wu, Yu H. ^{[1
]}

机构：

[1] Northwestern Univ, Dept Biomed Engn, Evanston, IL 60208 USA

[2] Lilly Res Labs, Diabet Res, Indianapolis, IN 46285 USA

[3] Univ Chicago, Dept Med, Div Biol Sci, Chicago, IL 60637 USA

[4] Rehabil Inst Chicago, Chicago, IL 60611 USA

来源：

SCIENTIFIC REPORTS | 2013年 / 3卷

基金：

美国国家科学基金会;

关键词：

ENDOTHELIAL PROGENITOR CELLS; ARTERIAL ELASTIC LAMINAE; REPERFUSION INJURY; BONE-MARROW; BETA-KLOTHO; PPAR-ALPHA; C-KIT; ACTIVATION; SURVIVAL; AKT;

D O I：

10.1038/srep02767

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Myocardial ischemia, while causing cardiomyocyte injury, can activate innate protective processes, enhancing myocardial tolerance to ischemia. Such processes are present in not only the heart, but also remote organs. In this investigation, we demonstrated a cardioprotective process involving FGF21 from the liver and adipose tissue. In response to myocardial ischemia/reperfusion injury in the mouse, FGF21 was upregulated and released from the hepatic cells and adipocytes into the circulation and interacted with FGFR1 in cardiomyocytes under the mediation of the cell membrane protein beta-Klotho, inducing FGFR1 phosphorylation. This action caused phosphorylation of the signaling molecules PI3K p85, Akt1, and BAD, thereby reducing caspase 3 activity, cell death, and myocardial infarction in association with improvement of myocardial function. These observations suggest that FGF21 is upregulated and released from the liver and adipose tissue in myocardial injury, contributing to myocardial protection by the mediation of the FGFR1/beta-Klotho-PI3K-Akt1-BAD signaling network.

引用

页数：11

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