MiR-424 prevents astrogliosis after cerebral ischemia/reperfusion in elderly mice by enhancing repressive H3K27me3 via NFIA/DNMT1 signaling

The FEBS Journal
Haiping ZhaoYumin Luo

Abstract

Global DNA and histone methylation patterns in astrocytes following ischemia are influenced by age; however, it is unknown whether aberrant methylation can induce reactive astrogliosis after ischemic stroke in elderly rodents. Here we showed that phosphorylated signal transducer and activator of transcription 3 (STAT3) level increased along with that of the astrogliosis marker glial fibrillary acidic protein (GFAP) on days 1, 3, and 14 post-reperfusion in 9-month-old male mice with middle cerebral artery occlusion (MCAO). Methylation of the STAT3 binding site in the GFAP gene promoter was increased in these mice on days 3 and 14 postreperfusion. The repressive modification histone 3 lysine 27 trimethylation (H3K27me3) was decreased, whereas the permissive modification histone 3 lysine 4 trimethylation was increased in GFAP-positive cells in the ipsilateral cortex. Furthermore, DNA methyltransferase 1 (DNMT1) expression in astrocytes was upregulated in the ischemic brain. In primary astrocyte cultures, the microRNA miR-424 was found to target nuclear factor IA (NFIA); miR-424 agomir increased DNMT1 and H3K27me3 levels in U87 cells subjected to oxygen and glucose deprivation and induced cell cycle arrest in primary astrocytes whi...Continue Reading

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Citations

Apr 3, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Fangfang LiYumin Luo
Mar 1, 2020·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Kai ZhongYi-Lu Ye
Jul 22, 2021·Cancer Biotherapy & Radiopharmaceuticals·Chao YangWei Lu
Sep 3, 2021·Journal of Physiology and Biochemistry·Yaxin SuZhongcheng Wang

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