TAK1 may promote the development of diabetic nephropathy by reducing the stability of SnoN protein
TAK1 may promote the development of diabetic nephropathy by reducing the stability of SnoN protein
复制标题
TAK1可能通过降低SnoN蛋白的稳定性促进糖尿病肾病的发生
DOI：
10.1016/j.lfs.2019.04.058
复制
发表时间：
2019-07-01
期刊：
影响因子：
6.1
通讯作者：
Guo, Bing
中科院分区：
文献类型：
--
作者：
Wang, Yuanyuan;Mao, Yanwen;Guo, Bing
目的：本研究旨在探讨转化生长因子β激活蛋白激酶1（transforminggrowthfactor-beta-activatedproteinkinase1，TAK1）对糖尿病肾病（diabeticnephropathy，DN）发生、发展的影响。该研究确定了调节TAK1的表达或活性对SnoN蛋白水平的影响及其对上皮-间充质转化（EMT）和细胞外基质（ECM）沉积的影响。在高糖条件下，TGF-β 1/TAK1诱导的SnoN蛋白磷酸化和泛素化的激活导致SnoN蛋白水平降低，这是SnoN降解增强的结果，其促进肾小管上皮细胞中EMT和ECM的沉积。研究表明TAK1通过降低SnoN蛋白的稳定性，降低SnoN蛋白水平。意义：TAK1介导SnoN磷酸化，导致SnoN泛素化并最终降解，从而促进EMT和ECM沉积，促进DN时肾纤维化。
Aims: This study aimed to investigate the role of transforming growth factor-beta-activated protein kinase 1(TAK1) in the development of diabetic nephropathy (DN) by regulating the protein stability of Ski-related novel protein N(SnoN).Main methods: A combination of in vivo and in vitro model systems was used to investigate how TAK1 regulated the expression of SnoN protein in DN. The study determined the effects of modulating the expression or activity of TAK1 on the SnoN protein level and its influence on the epithelial-mesenchymal transition (EMT) and extracellular matrix (ECM) deposition.Key findings: Under the high-glucose condition, the activation of TGF-beta 1/TAK1-induced phosphorylation and ubiquitination of SnoN protein resulted in reduced SnoN protein level as a consequence of enhanced SnoN degradation, which promoted EMT and ECM deposition in renal tubular epithelial cells. The study showed that TAK1 impaired SnoN protein level by decreasing the protein stability of SnoN.Significance: TAK1 mediated the phosphorylation of SnoN, resulting in SnoN ubiquitination and eventual degradation, which enhanced EMT and ECM deposition to promote renal fibrosis during DN.