Mol Med Rep.2020 Mar;21(3):1145-1153.doi: 10.3892/mmr.2019.10903. Epub 2019 Dec 23.

miR‑222 regulates brain injury and inflammation following intracerebral hemorrhage by targeting ITGB8

Yan-Yan Bai  1 Jun-Zhi Niu  2 Affiliations

Free PMC article

Abstract

Intracerebral hemorrhage (ICH) is a disease associated with high mortality and morbidity. MicroRNAs (miRNAs) have been reported to be associated with the pathogenesis of numerous cerebrovascular diseases, including ICH. miR‑222 has been revealed to play important roles in various physiological and pathological processes in cardiovascular diseases. However, its role in ICH remains largely unknown. The aim of the present study was to evaluate the potential effect of miR‑222 on brain injury in ICH. The results revealed that the expression of miR‑222 was significantly increased in ICH, and downregulation of miR‑222 significantly reduced erythrocyte lysate‑induced cell apoptosis by decreasing the levels of cleaved caspase‑3, cleaved caspase‑9 and Bax and increasing the level of Bcl‑2. In addition, downregulation of miR‑222 suppressed the inflammatory responses in erythrocyte lysate‑induced microglia, and inhibited inflammation, brain water content and improved neurological functions in ICH mice. Mechanistically, integrin subunit β8 (ITGB8) was identified as a direct target of negative regulation by miR‑222 in microglia cells, and up‑regulation of ITGB8 led to the attenuation of inflammation and apoptosis. Collectively, the present findings indicated that miR‑222 was a crucial regulator of inflammation via targeting of ITGB8, and represented a promising therapeutic strategy for ICH.

Keywords: microrna-222; intracerebral hemorrhage; inflammatory; apoptosis; integrin subunit β8.

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