SnoN upregulation ameliorates renal fibrosis in diabetic nephropathy.
SnoN upregulation ameliorates renal fibrosis in diabetic nephropathy.
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SnoN 上调可改善糖尿病肾病的肾纤维化
DOI：
10.1371/journal.pone.0174471
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Guo B
中科院分区：
文献类型：
--
作者：
Liu L;Shi M;Wang Y;Zhang C;Su B;Xiao Y;Guo B
在糖尿病肾病进展过程中，SnoN的逐渐减少与TGF-β1的逐渐升高相关，表明SnoN可能是TGF-β1信号传导的介导者，对TGF- β1诱导的肾纤维化具有潜在的治疗益处。为了表征SnoN在肾纤维化中的作用，我们评估了响应于高糖应激的SnoN表达模式，并评估了上调SnoN对肾纤维化的影响。高糖应激诱导SnoN、TGF-β1和Arkadia转录显著升高;然而，在这些条件下观察到SnoN蛋白水平显著降低。通过Arkadia敲低实现SnoN蛋白的上调，这导致肾小管细胞中高葡萄糖诱导的上皮-间充质转化（EMT）受到抑制，这是肾纤维化的起始阶段。或者，EMT被显性表达的外源SnoN抑制而不干扰TGF-β1。总体而言，肾脏SnoN上调通过缓解高糖诱导的EMT来改善肾纤维化;这些发现支持了针对SnoN治疗糖尿病肾病的转化方法。
Progressive reduction of SnoN is associated with gradual elevation of TGF-β1 during diabetic nephropathy progression, suggesting SnoN to be a possible mediator of TGF-β1 signaling, with potential therapeutic benefits against TGF- β1 –induced renal fibrosis. To characterize SnoN for its role in renal fibrosis, we assessed SnoN expression patterns in response to high glucose stress, and evaluated the effects of upregulating SnoN on renal fibrosis. High glucose stress induced significantly elevated SnoN, TGF-β1, and Arkadia transcription; however, significantly reduced SnoN protein levels were observed under these conditions. Upregulating the SnoN protein was achieved by Arkadia knockdown, which resulted in inhibited high glucose-induced epithelial-mesenchymal transition (EMT) in renal tubular cells, the onset phase of renal fibrosis. Alternatively, EMT was suppressed by dominantly expressed exogenous SnoN without interfering with TGF-β1. Overall, renal SnoN upregulation ameliorates renal fibrosis by relieving high glucose-induced EMT; these findings support a translational approach targeting SnoN for the treatment of diabetic nephropathy.