MiR-702-5p ameliorates diabetic encephalopathy in db/db mice by regulating 12/15-LOX
作者全名："Tu, Yujun; Chen, Qi; Guo, Wenjia; Xiang, Pu; Huang, Haifeng; Fei, Huizhi; Chen, Lin; Yang, Yang; Peng, Zhe; Gu, Chao; Tan, Xiaodan; Liu, Xia; Lu, Yi; Chen, Rongchun; Wang, Hong; Luo, Ying; Yang, Junqing"
作者地址："[Tu, Yujun; Guo, Wenjia; Xiang, Pu; Huang, Haifeng; Fei, Huizhi; Chen, Lin; Yang, Yang; Peng, Zhe; Gu, Chao; Tan, Xiaodan; Liu, Xia; Lu, Yi; Chen, Rongchun; Wang, Hong; Luo, Ying; Yang, Junqing] Chongqing Med Univ, Key Lab Biochem & Mol Pharmacol, Dept Pharmacol, Chongqing 400016, Peoples R China; [Chen, Qi] GuiZhou Prov Peoples Hosp, Dept Pharm, Guiyang 550000, Peoples R China; [Xiang, Pu] Dianjiang Peoples Hosp Chongqing, Chongqing 408300, Peoples R China"
通信作者："Yang, JQ (通讯作者)，Chongqing Med Univ, Dept Pharmacol, 1 Med Coll Rd, Chongqing, Peoples R China."
ESI学科分类：NEUROSCIENCE & BEHAVIOR
关键词：iabetic encephalopathy; miR-702-5p; 12/15-LOX; hippocampus; HT22
摘要："The purpose of this study was to investigate the effect of miR-702-5p on diabetic encephalopathy (DE) and the interaction of miR-702-5p/12/15-LOX in the central nervous system (CNS). In this study, db/db mice were used as DE animal model and HT22 cells were treated with high-glucose (HG). Based on the bioinformatics prediction of possible binding sites between miR-702-5p and 12/15-LOX, we found that the expression of miR-702-5p was significantly down-regulated while 12/15-LOX up-regulated in vivo and in vitro, and the expression changes were inversely correlated. In vivo, diabetic mice with cognitive dysfunction and hippocampal neuronal damage had a concomitant increase in amyloid precursor protein (APP), amyloid beta(A beta), tau, BAX protein expressions; by contrast, Bcl-2 protein expression was significantly decreased. Overexpression of miR-702-5p significantly reduced the histopathological damage of the hippocampus, improved the learning and memory function of db/db mice, down-regulated 12/15-LOX, APP, A beta, tau, BAX protein expressions significantly and up-regulated the expression of Bcl-2. In vitro, miR-702-5p mimic reversed the decline in cell viability and the increase in cell apoptosis induced by HG. Simultaneously, reduced 12/15-LOX, APP, A beta, BAX protein expressions, and increased Bcl-2 protein expression were detected in the miR-702-5p mimic group. Moreover, combined administration of miR-702-5p mimic and 12/15-LOX overexpression lentivirus significantly reversed the protective effect of up-regulation of miR-702-5p. In conclusion, miR-702-5p has a neuroprotective effect on DE, and this effect was achieved by inhibiting 12/15-LOX. However, miR-702-5p had an endogenous regulatory effect on 12/15-LOX rather than a direct targeting relationship."
基金机构：Science and Technology Foundation of Guizhou Province (QKH) [1191]
基金资助正文：Acknowledgement is given to the Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology for providing an experimental platform. The study was approved by the Science and Technology Foundation of Guizhou Province (QKH1191).