OIP5-AS1 Attenuates Microangiopathy in Diabetic Mouse by Regulating miR-200b/ACE2.

OBJECTIVE:This study aimed to investigate OIP5-AS1 effects on microangiopathy in diabetic mouse. METHODS:The expression levels of OIP5-AS1, miR-200b, and ACE2 expression were measured by RT-qPCR. Western blot was conducted to detect The ACE2 and Ang-(1-7) expression. Luciferase reporter assays were used to identify the interaction between miR-200b and OIP5-AS1 or ACE2. Morris water maze test was performed for detecting cognitive function. RESULTS:Our results indicated that diabetic mice exhibited much lower OIP5-AS1 expression in the hippocampus than normal mice. Diabetic mice of OIP5-AS1 KO group showed remarkably lower OIP5-AS1 expression in the hippocampus, longer escape latency and lower percentage of CD31+ cells in the hippocampusthan those of WT group. OIP5-AS1 knockdown directly up-regulated miR-200b expression and ACE2 was directly inhibited by miR-200b. Relative to normal mice, diabetic mice had markedly higher miR-200b expression and lower ACE2 expression in the hippocampus. Diabetic mice of OIP5-AS1 KO group were with obviously higher miR-200b expression and lower ACE2 expression in the hippocampus than those of WT group. Compared with diabetic mice of OIP5-AS1 KO group, those of WT group, OIP5-AS1 KO + miR-200b inhibitor group and OIP5-AS1 KO + ACE2 group had obviously shorter escape latency and higher percentage of CD31⁺ cells and more caspase-3 protein expression in the hippocampus. CONCLUSIONS:OIP5-AS1 attenuated microangiopathy in diabetic mouse by regulating miR-200b/ACE2.

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