FGF13 Is a Novel Regulator of NF-κB and Potentiates Pathological Cardiac Hypertrophy.
FGF13 Is a Novel Regulator of NF-κB and Potentiates Pathological Cardiac Hypertrophy.
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FGF13 是 NF-kappa B 的新型调节剂，可增强病理性心脏肥大
DOI：
10.1016/j.isci.2020.101627
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发表时间：
2020-10-23
期刊：
影响因子：
5.8
通讯作者：
Li X
中科院分区：
文献类型：
--
作者：
Sun J;Niu C;Ye W;An N;Chen G;Huang X;Wang J;Chen X;Shen Y;Huang S;Wang Y;Wang X;Wang Y;Jin L;Cong W;Li X
FGF13是细胞内FGF因子。其在心肌病中的作用很少被研究。我们发现内源性FGF13在心脏肥厚中上调，并伴有核定位增加。FGF13的上调在肥厚心肌细胞和小鼠心脏中都起着恶化的作用。在机制上，FGF13通过其核定位序列直接与p65相互作用，并在心肌肥厚的细胞核中与p65共定位。在iso处理的nrcm和tac手术小鼠心脏中，FGF13缺乏抑制NF-κB的激活，而FGF13过表达则呈现相反的趋势。此外，仅FGF13过表达就足以激活心肌细胞中的NF-κB。FGF13与p65的相互作用或FGF13对NF-κB的影响与i -κB无关。总之，在基础和应激条件下心肌细胞中发现了一种不依赖于i -κB的NF-κB调节机制，这表明FGF13有望作为病理性心肌肥大和心力衰竭的治疗靶点。内源性FGF13在压力过载心肌细胞中上调FGF13直接与p65相互作用强迫FGF13过表达激活心肌细胞病理生理中的NF-κB；细胞生物学
FGF13 is an intracellular FGF factor. Its role in cardiomyopathies has been rarely investigated. We revealed that endogenous FGF13 is up-regulated in cardiac hypertrophy accompanied by increased nuclear localization. The upregulation of FGF13 plays a deteriorating role both in hypertrophic cardiomyocytes and mouse hearts. Mechanistically, FGF13 directly interacts with p65 by its nuclear localization sequence and co-localizes with p65 in the nucleus in cardiac hypertrophy. FGF13 deficiency inhibits NF-κB activation in ISO-treated NRCMs and TAC-surgery mouse hearts, whereas FGF13 overexpression shows the opposite trend. Moreover, FGF13 overexpression alone is sufficient to activate NF-κB in cardiomyocytes. The interaction between FGF13 and p65 or the effects of FGF13 on NF-κB have nothing to do with IκB. Together, an IκB-independent mechanism for NF-κB regulation has been revealed in cardiomyocytes both under basal and stressful conditions, suggesting the promising application of FGF13 as a therapeutic target for pathological cardiac hypertrophy and heart failure. Endogenous FGF13 is up-regulated in cardiomyocytes under pressure overload FGF13 directly interacts with p65 Forced FGF13 overexpression activates NF-κB in cardiomyocytes Pathophysiology; Cell Biology
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DOI：
10.1016/j.ijcha.2016.03.007
发表时间：
2016-06
期刊：
International journal of cardiology. Heart & vasculature
影响因子：
--
作者：
Furihata T;Kinugawa S;Takada S;Fukushima A;Takahashi M;Homma T;Masaki Y;Tsuda M;Matsumoto J;Mizushima W;Matsushima S;Yokota T;Tsutsui H
通讯作者：
Tsutsui H
影响因子：
20.1
作者：
Ackers-Johnson M;Li PY;Holmes AP;O'Brien SM;Pavlovic D;Foo RS
通讯作者：
Foo RS
影响因子：
20.1
作者：
Hennessey JA;Wei EQ;Pitt GS
通讯作者：
Pitt GS
影响因子：
37.8
作者：
Hulot JS;Fauconnier J;Ramanujam D;Chaanine A;Aubart F;Sassi Y;Merkle S;Cazorla O;Ouillé A;Dupuis M;Hadri L;Jeong D;Mühlstedt S;Schmitt J;Braun A;Bénard L;Saliba Y;Laggerbauer B;Nieswandt B;Lacampagne A;Hajjar RJ;Lompré AM;Engelhardt S
通讯作者：
Engelhardt S
影响因子：
56.9
作者：
BROWN, K;GERSTBERGER, S;SIEBENLIST, U
通讯作者：
SIEBENLIST, U