Loss of TRADD attenuates pressure overload-induced cardiac hypertrophy through regulating TAK1/P38 MAPK signalling in mice.
Loss of TRADD attenuates pressure overload-induced cardiac hypertrophy through regulating TAK1/P38 MAPK signalling in mice.
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TRADD 的缺失通过调节小鼠体内的 TAK1/P38 MAPK 信号传导来减轻压力超负荷引起的心脏肥大。
DOI：
10.1016/j.bbrc.2016.12.104
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Yang Xiangjun
中科院分区：
文献类型：
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作者：
Wu Lianpin;Cao Zhiyong;Mei Liqin;Ji Ling;Jin Qike;Zeng Jingjing;Lin Jiafeng;Chu Maoping;Li Lei;Yang Xiangjun
我们研究了肿瘤坏死因子受体（TNFR）相关死亡结构域（TRADD）的作用，压力超负荷诱导的心肌肥厚和潜在的分子机制，通过使用TRADD缺陷小鼠模型。6-8将野生型和TRADD敲除小鼠进行横主动脉缩窄（TAC）或假手术（每组6-8只小鼠）。TAC后14天，通过超声心动图以及心脏样本的病理和分子分析来测量心脏功能。qPCR检测心肌肥厚和纤维化标志物的表达。磷酸化和总TAK 1，Akt，和p38 MAPK水平通过蛋白质印迹法进行了检查。TAC后，TRADD敲除（KO）小鼠的肺、心/体重比值、左心室壁厚/室径比值和心肌细胞横截面积均显著低于野生型小鼠。此外，心脏肥大和纤维化标志物下调TRADD敲除小鼠比野生型小鼠后TAC。蛋白表达分析显示，TAC后野生型和TRADD KO小鼠磷酸化TAK 1、p38 MAPK和AKT表达均上调，TRADD缺陷后TAK 1和p38 MAPK磷酸化水平降低更明显，而TAC后TRADD KO和野生型小鼠磷酸化AKT表达相似。我们的数据表明，TRADD KO通过介导TAK 1/p38 MAPK而不是AKT磷酸化来减弱小鼠中压力超负荷诱导的心脏肥大。
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.