Carboxy-terminal modulator protein attenuated extracellular matrix deposit by inhibiting phospho-Akt, TGF-β1 and α-SMA in kidneys of diabetic mice
Carboxy-terminal modulator protein attenuated extracellular matrix deposit by inhibiting phospho-Akt, TGF-β1 and α-SMA in kidneys of diabetic mice
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羧基末端调节蛋白通过抑制糖尿病小鼠肾脏中的磷酸-Akt、TGF-β1 和 α-SMA 来减弱细胞外基质沉积
DOI：
10.1016/j.bbrc.2016.05.032
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发表时间：
2016-06-10
影响因子：
3.1
通讯作者：
Duan, Huijun
中科院分区：
文献类型：
--
作者：
Chen, Ning;Hao, Jun;Duan, Huijun
肾小球硬化、肾小管间质细胞外基质存款和纤维化是糖尿病肾病的主要特征，其发生与PI 3 K/Akt信号通路的激活有关。羧基末端调节蛋白（Carboxy-terminal modulator protein，CTMP）是PI 3 K/Akt信号通路的负调控因子。CTMP是否调节糖尿病肾病肾脏细胞外基质代谢尚不清楚。在此，在糖尿病小鼠中发现肾CTMP减少，磷酸化Akt（Ser 473）、TGF-β 1、α-SMA和细胞外基质存款增加。此外，在培养的人肾近端小管上皮细胞（HKC）中，高糖降低CTMP表达，伴随着增强的磷酸化Akt（Ser 473）、TGF-β 1和α-SMA，这通过转染pYr-ads-4-musCTMP载体有效地防止。此外，与接受pYr-adshuttle-4载体的糖尿病小鼠相比，通过尾静脉将pYr-ads-4-musCTMP载体递送到糖尿病小鼠的肾脏中使CTMP表达增加8.84倍，随后磷酸化Akt（Ser 473）、TGF-β 1和α-SMA降低60.00%、76.50%和24.37%。同样，糖尿病小鼠增加的肾细胞外基质积累也被pYr-ads-4-mu 5CTMP载体的递送抑制。CTMP通过调节Akt磷酸化、TGF-β 1和α-SMA的表达，减轻糖尿病小鼠肾脏细胞外基质存款。(C)2016 Elsevier Inc. All rights reserved.
Glomerulosclerosis and tubular interstitial extracellular matrix deposit and fibrosis are the main features of diabetic nephropathy, which are mediated by activation of PI3K/Akt signal pathway. Carboxy-terminal modulator protein (CTMP) is known as a negative regulator of PI3K/Akt pathway. Whether CTMP regulates renal extracellular matrix metabolism of diabetic nephropathy is still not known. Here, renal decreased CTMP, enhanced phospho-Akt (Ser 473), TGF-beta 1, alpha-SMA and extracellular matrix deposit are found in diabetic mice. Furthermore, high glucose decreases CTMP expression accompanied by enhanced phospho-Akt (Ser 473), TGF-beta 1 and alpha-SMA in cultured human renal proximal tubular epithelial cells (HKC), which are effectively prevented by transfection of pYr-ads-4-musCTMP vector. Moreover, delivery of pYr-ads-4-musCTMP vector into kidneys via tail vein of diabetic mice increases CTMP expression by 8.84 times followed by 60.00%, 76.50% and 24.37% decreases of phospho-Akt (Ser 473), TGF-beta 1 and alpha-SMA compared with diabetic mice receiving pYr-adshuttle-4 vector. Again, increased renal extracellular matrix accumulation of diabetic mice is also inhibited with delivery of pYr-ads-4-mu5CTMP vector. Our results indicate that CTMP attenuates renal extracellular matrix deposit by regulating the phosphorylation of Akt, TGF-beta 1 and alpha-SMA expression in diabetic mice. (C) 2016 Elsevier Inc. All rights reserved.