MicroRNA-130a regulates cerebral ischemia-induced blood-brain barrier permeability by targeting Homeobox A5.

Abstract

Blood-brain barrier (BBB) disruption plays a critical role in brain injury induced by cerebral ischemia, and preserving BBB integrity during ischemia could alleviate cerebral injury. We examined the role of miR-130a in ischemic BBB disruption by using models of rat middle cerebral artery occlusion and cell oxygen-glucose deprivation. We found that ischemia significantly increased microRNA-130a (miR-130a) level and that miR-130a was predominantly from brain microvascular endothelial cells. Antagomir-130a, an antagonist of miR-130a, could attenuate brain edema, lower BBB permeability, reduce infarct volume, and improve neurologic function. MiR-130a overexpression induced by miR-130a mimic increased monolayer permeability, and intercellular inhibition of miR-130a by a miR-130a inhibitor suppressed oxygen-glucose deprivation-induced increase in monolayer permeability. Moreover, dual luciferase reporter system showed that Homeobox A5 was the direct target of miR-130a. MiR-130a, by inhibiting Homeobox A5 expression, could down-regulate occludin, thereby increasing BBB permeability. Our results suggested that miR-130a might be implicated in ischemia-induced BBB dysfunction and serve as a target for the treatment of ischemic stroke.-Wang, Y., Wang, M.-D., Xia, Y.-P., Gao, Y., Zhu, Y.-Y., Chen, S.-C., Mao, L., He, Q.-W., Yue, Z.-Y., Hu, B. MicroRNA-130a regulates cerebral ischemia-induced blood-brain barrier permeability by targeting Homeobox A5.

• Authors: Yong Wang, Meng-Die Wang, Yuan-Peng Xia, Yuan Gao, Yi-Yi Zhu, Sheng-Cai Chen, Ling Mao, Quan-Wei He, Zhen-Yu Yue, Bo Hu
• Journal: FASEB journal : official publication of the Federation of American Societies for Experimental Biology (FASEB J) Vol. 32 Issue 2 Pg. 935-944 (02 2018) ISSN: 1530-6860 [Electronic] United States
• PMID: 29070584 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Homeodomain Proteins
• MIRN130 microRNA, rat
• MicroRNAs
• Occludin
• Ocln protein, rat
• Oligonucleotides

Topics

• Animals
• Blood-Brain Barrier (metabolism, pathology)
• Brain Ischemia (genetics, metabolism, pathology)
• Homeodomain Proteins (genetics, metabolism)
• Male
• MicroRNAs (antagonists & inhibitors, genetics, metabolism)
• Occludin (biosynthesis, genetics)
• Oligonucleotides (pharmacology)
• Permeability
• Rats
• Rats, Sprague-Dawley