MicroRNA‐182 exacerbates blood‐brain barrier (BBB) disruption by downregulating the mTOR/FOXO1 pathway in cerebral ischemia. Issue 10 (17th August 2020)

• Record Type: Journal Article
• Authors: Zhang, Tongshuai; Tian, Chao; Wu, Jinrong; Zhang, Yao; Wang, Jinghua; Kong, Qingfei; Mu, Lili; Sun, Bo; Ai, Tianhong; Wang, Yue; Zhao, Wei; Wang, Dandan; Li, Hulun; Wang, Guangyou
• Is Part Of: FASEB journal. Volume 34:Issue 10(2020)
• Page Start: 13762
• Page End: 13775
• Publication Date: 2020-08-17
• Subjects: BBB -- FOXO1 -- miR‐182 -- mTOR -- TJ proteins; Biology -- Periodicals; Biology, Experimental -- Periodicals; 570
• DOI: 10.1096/fj.201903092R
• Languages: English
• ISSNs: 0892-6638

Abstract

Abstract: Cerebral ischemia causes damage to the structure and function of the blood‐brain barrier (BBB) and alleviating BBB destruction will be of great significance for the treatment and prognosis of ischemic stroke. Recently, microRNAs have been shown to play a critical role in BBB integrity. However, the potential mechanism by which microRNA‐182 (miR‐182) affects the BBB in ischemic stroke remains unclear. We demonstrated for the first time that cerebral ischemia leads to a significant progressive increase in miR‐182 after pMCAO, and bEnd.3 cells are the primary target cells of miR‐182. In miR‐182 KD transgenic mice, infarct volume, and BBB permeability were attenuated, and tight junction (TJ) proteins increased. Inhibition of miR‐182 with an antagomir reduced OGD‐induced apoptosis of bEnd.3 cells and the loss of ZO‐1 and Occludin. To further explore the mechanism by which miR‐182 regulates BBB integrity, we detected the apoptotic proteins Bcl‐2/Bax and demonstrated that mTOR and FOXO1 were the targets of miR‐182. Inhibition of mTOR/FOXO1 by rapamycin/AS1842856 decreased the ratio of Bcl‐2/Bax and exacerbated TJ protein loss. Taken together, inhibition of miR‐182 protects BBB integrity by reducing endothelial cell apoptosis through the mTOR/FOXO1 pathway. Thus, miR‐182 may be a potential target for the treatment of BBB disruption during cerebral ischemia.