MicroRNA-338-5p alleviates cerebral ischemia/reperfusion injury by targeting connective tissue growth factor through the adenosine 5'-monophosphate-activated protein kinase/mammalian target of rapamycin signaling pathway.

Abstract

Cerebral ischemia/reperfusion (CIR) injury could lead to the function of brain cell disorder and cerebral infarction. MicroRNAs (miRNAs) have been reported to participate in the progression and protection of CIR injury. Thus, our study aimed to investigate the functional effects of microRNA-338-5p (miR-338-5p) on proliferation, apoptosis, and inflammatory response of CIR injury. According to the results, miR-338-5p was downregulated in the brain of the mice caused by CIR injury, and overexpression of miR-338-5p reduced the neurological deficit and infarct volume of the brain in the mice caused by CIR injury. Meanwhile, miR-338-5p overexpression promoted the proliferation, while suppressed the apoptosis and the inflammatory response of Neuro-2a cells exposed to hypoxia/reoxygenation (H/R). Interestingly, miR-338-5p directly targeted connective tissue growth factor (CTGF) and overexpression of CTGF reversed the functional effects of miR-338-5p on proliferation, apoptosis, and inflammatory response in Neuro-2a cells caused by H/R. More importantly, miR-338-5p affected the adenosine 5¢-monophosphate (AMP)-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling pathway by regulating CTGF expression in Neuro-2a cells exposed to H/R. Taken together, we concluded that MiR-338-5p promoted the proliferation, while suppressed the apoptosis and the inflammatory response of cells exposed to H/R by targeting CTGF through the AMPK/mTOR signaling pathway.