FGF1(ΔHBS) prevents diabetic cardiomyopathy by maintaining mitochondrial homeostasis and reducing oxidative stress via AMPK/Nur77 suppression.
FGF1(ΔHBS) prevents diabetic cardiomyopathy by maintaining mitochondrial homeostasis and reducing oxidative stress via AMPK/Nur77 suppression.
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FGF1(Delta HBS) 通过维持线粒体稳态并通过 AMPK/Nur77 抑制减少氧化应激来预防糖尿病心肌病
DOI：
10.1038/s41392-021-00542-2
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发表时间：
2021-03-24
影响因子：
39.3
通讯作者：
Huang Z
中科院分区：
文献类型：
--
作者：
Wang D;Yin Y;Wang S;Zhao T;Gong F;Zhao Y;Wang B;Huang Y;Cheng Z;Zhu G;Wang Z;Wang Y;Ren J;Liang G;Li X;Huang Z
成纤维细胞生长因子1（fibroblast growth factor 1，FGF 1）是一种经典的促分裂原，具有多种功能，如代谢调节、心肌保护等。在这里，我们发现，血清中的FGF 1水平下降，并与分数缩短糖尿病心肌病（DCM）患者，表明FGF 1是一个潜在的治疗靶点DCM。我们发现，用具有降低的增殖能力的FGF 1变体（FGF 1 β HBS）治疗可以预防糖尿病诱导的心脏损伤和重塑，并恢复心脏功能。从db/db小鼠的心脏组织获得的RNA-Seq结果显示，通过FGF 1 α HBS处理，抗氧化基因的表达水平显著增加，Nur 77的表达水平降低。体内和体外研究均表明，FGF 1 α HBS通过显著减少线粒体碎片化、活性氧（ROS）产生和细胞色素c渗漏以及以5'AMP活化蛋白激酶（AMPK）/Nur 77依赖性方式增强线粒体呼吸速率和β-氧化来发挥这些有益作用，所有这些在AMPK缺失小鼠中均未观察到。FGF 1 α HBS有利的代谢活性和降低的增殖特性证明了其用于治疗DCM和其他代谢紊乱的有希望的潜力。
As a classically known mitogen, fibroblast growth factor 1 (FGF1) has been found to exert other pleiotropic functions such as metabolic regulation and myocardial protection. Here, we show that serum levels of FGF1 were decreased and positively correlated with fraction shortening in diabetic cardiomyopathy (DCM) patients, indicating that FGF1 is a potential therapeutic target for DCM. We found that treatment with a FGF1 variant (FGF1∆HBS) with reduced proliferative potency prevented diabetes-induced cardiac injury and remodeling and restored cardiac function. RNA-Seq results obtained from the cardiac tissues of db/db mice showed significant increase in the expression levels of anti-oxidative genes and decrease of Nur77 by FGF1∆HBS treatment. Both in vivo and in vitro studies indicate that FGF1∆HBS exerted these beneficial effects by markedly reducing mitochondrial fragmentation, reactive oxygen species (ROS) generation and cytochrome c leakage and enhancing mitochondrial respiration rate and β-oxidation in a 5’ AMP-activated protein kinase (AMPK)/Nur77-dependent manner, all of which were not observed in the AMPK null mice. The favorable metabolic activity and reduced proliferative properties of FGF1∆HBS testify to its promising potential for use in the treatment of DCM and other metabolic disorders.
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影响因子：
10.8
作者：
Formiga, Fabio R.;Pelacho, Beatriz;Blanco-Prieto, Maria J.
通讯作者：
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影响因子：
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作者：
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通讯作者：
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