Loss of TRADD attenuates pressure overload-induced cardiac hypertrophy through regulating TAK1/P38 MAPK signalling in mice

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• 作者：Lianpin Wu^a ; ^b ; ¹ ; Zhiyong Cao^c ; ¹ ; Ling Ji^d ; Liqin Mei^e ; Qike Jin^b ; Jingjing Zeng^b ; Jiafeng Lin^b ; Maoping Chu^b ; Lei Li^b ; ^{lileiii@yahoo.com} ; Xiangjun Yang^a ; ^{th.reestonee@gmail.com}
• 关键词：TAK1 ; Pressure overload ; TRADD ; Cardiac hypertrophy
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2017
• 出版时间：5 February 2017
• 年：2017
• 卷：483
• 期：2
• 页码：810-815
• 全文大小：1014 K
• 卷排序：483

文摘

We investigated the role of tumour necrosis factor receptor (TNFR)-associated death domain (TRADD) on pressure overload-induced cardiac hypertrophy and the underlying molecular mechanisms by using a TRADD deficiency mice model. 6–8 weeks wild-type and TRADD knockout mice were performed to transverse aorta constriction (TAC) or sham operation (6–8 mice for each group). 14 days after TAC, cardiac function was measured by echocardiography, as well as by pathological and molecular analyses of heart samples. The expressions of cardiac hypertrophic and fibrotic markers were detected by qPCR. Phosphorylated and total TAK1, Akt, and p38 MAPK levels were examined by Western blotting. The ratios of lung or heart/body weight, wall thickness/chamber diameter of left ventricular and cross area of cardiomyocyte were significantly reduced in TRADD knockout (KO) mice than those of wild-type mice after TAC. Moreover, cardiac hypertrophic and fibrotic markers were downregulated in TRADD knockout mice than those of wild-type mice following TAC. Protein expression analysis showed phosphorylated TAK1, p38 MAPK and AKT were upregulated after TAC in both wild-type and TRADD KO mice, phosphorylation of TAK1 and p38 MAPK was reduced more remarkably after TRADD deficiency, while phosphorylated AKT expression was similar between TRADD KO and wild-type mice following TAC. Our data suggest that TRADD KO blunts pressure overload-induced cardiac hypertrophy through mediating TAK1/p38 MAPK but not AKT phosphorylation in mice.