miR-1252通过靶向调控TGF-β1-PI3K/Akt通路对高糖诱导的心肌纤维化的保护作用的机制

Mechanism of miR-1252 Protective Effect on High Glucose-induced Myocardial Fibrosis by Targeted Regulation of TGF-β1-PI3K/Akt Pathway

为了探讨miR-1252对高糖诱导的心肌纤维化的保护作用的机制,本研究通过小鼠的心脏的组化切片分析miR-1252敲除对糖尿病和正常小鼠心肌纤维化的影响,并且通过Western-blotting实验研究miR-1252调控高糖诱导的心肌纤维化的信号通路。结果表明:糖尿病且miR-1252敲除的小鼠心肌纤维化程度最高,且miR-1252敲除的成纤维细胞TGF-β1表达增高,TGF-β1能上调LOX、Akt和p-Akt蛋白的表达,但是需要PI3K蛋白的存在。本研究结果初步说明,miR-1252能通过调控TGF-β1-PI3K/Akt信号通路抑制高糖诱导的心肌纤维化,且LOX是miR-1252主要的调控蛋白之一。

To explore the mechanism of miR-1252 protective effect on high glucose-induced myocardial fibrosis, we analyzed the effects of miR-1252 knockdown on myocardial fibrosis in diabetic and normal mice by histochemical sectioning of the mouse heart, and study on the signaling pathway of miR-1252 regulating high glucose-induced myocardial fibrosis by Western-blotting assay. The result showed that the miR-1252 knockout diabetic mice had the highest degree of myocardial fibrosis, and the expression of TGF-β1 in miR-1252 knockout fibroblasts was increased. TGF-β1 up-regulated the expression of LOX, Akt and p-Akt proteins. However, the presence of the PI3K protein is required. The finding spreliminary indicated that the miR-1252 should inhibit high glucose-induced myocardial fibrosis by regulating TGF-β1-PI3K/Akt signaling pathway, and LOX should be one of the major regulatory proteins of miR-1252.