MicroRNA‐149–5p regulates blood–brain barrier permeability after transient middle cerebral artery occlusion in rats by targeting S1PR2 of pericytes. Issue 6 (18th January 2018)

• Record Type: Journal Article
• Authors: Wan, Yan; Jin, Hui-Juan; Zhu, Yi-Yi; Fang, Zhi; Mao, Ling; He, Quanwei; Xia, Yuan-Peng; Li, Man; Li, Yanan; Chen, Xiaoqian; Hu1, Bo
• Is Part Of: FASEB journal. Volume 32:Issue 6(2018)
• Page Start: 3133
• Page End: 3148
• Publication Date: 2018-01-18
• Subjects: pericyte migration -- N-cadherin -- NF-κB p65 -- stroke; Biology -- Periodicals; Biology, Experimental -- Periodicals; 570
• DOI: 10.1096/fj.201701121R
• Languages: English
• ISSNs: 0892-6638

Abstract

ABSTRACT: Blood‐brain barrier (BBB) disruption caused by reperfusion injury after ischemic stroke is an intractable event conducive to further injury. Brain pericytes play a vital role in maintaining BBB integrity by interacting with other components of the BBB. In this study, we found that sphingosine‐1‐phosphate receptor (S1PR)2 expressed in pericytes was significantly up‐regulated after ischemia in vivo and in vitro. By using a S1PR2 antagonist (JTE‐013), we showed that S1PR2 plays a critical role in the induction of BBB permeability of transient middle cerebral artery occlusion (tMCAO) rats and the in vitro BBB model. Furthermore, we discovered that S1PR2 may decrease N‐cadherin expression and increase pericyte migration via NF‐κB p65 signal and found that S1PR2 could be regulated by miR‐149–5p negatively, which was decreased in the ischemic boundary zone and cultured pericytes after ischemia. Overexpression of miR‐149–5p in cultured pericytes substantially increased N‐cadherin expression and decreased pericyte migration, which decreased BBB leakage in the in vitro model. Up‐regulating miR‐149–5p by intracerebroventricular injection of agomir‐149–5p attenuated BBB permeability and improved the outcomes of tMCAO rats significantly. Thus, our data suggest that miR‐149–5p may serve as a potential target for treatment of BBB disruption after ischemic stroke.—Wan, Y., Jin, H.‐J., Zhu, Y.‐Y., Fang Z., Mao, L., He, Q., Xia, Y.‐P., Li, M., Li, Y., Chen, X., Hu, B. MicroRNA‐149–5p regulates blood‐brain barrier permeability after transient middle cerebral artery occlusion in rats by targeting S1PR2 of pericytes. FASEB J. 32, 3133–3148 (2018). www.fasebj.org