MiR-207/352 regulate lysosomal-associated membrane proteins and enzymes following ischemic stroke.

Abstract

The role of microRNAs (miRNAs) in lysosome-mediated neuronal death and survival following ischemic stroke remains unknown. Herein, using miRNA and mRNA gene expression profiling microarrays, we identified the differentially expressed 24 miRNAs and 494 genes in the cortical peri-infarct area, respectively. Integrating the miRNA targets and mRNA expression profiles, we found 47 genes of miRNA targets, including lysosomal-associated membrane protein 2 (LAMP2), Hexb, Bcl2, etc. MiR-207 and miR-352 were mainly downregulated after ischemic stroke, followed by a slight return to baseline during post-middle cerebral artery occlusion (MCAO) 1d to 7d. Furthermore, the luciferase reporter assay demonstrated that LAMP2 and Hexb were the direct targets of miR-207 and miR-352, respectively. After lateral ventricle injection with miR-207 agonist mimics, the neurological deficit scores and infarct volumes were attenuated, and the structure of mitochondria ridges was improved. In addition, miR-207 mimics could reduce the number of cellular lysosome and autophagosome, whereas increase the number of autophagic vacuoles, indicating miR-207 might affect the latter part of lysosomal-autophagy pathway and mitochondria-induced apoptosis. These results suggested that miR-207 and miR-352 were involved in lysosomal pathway for mediating ischemic injury and spontaneous recovery. MiR-207 mimics as potential target drugs could protect against autophagic cell death after ischemic stroke.

• Authors: J Tao, W Liu, G Shang, Y Zheng, J Huang, R Lin, L Chen
• Journal: Neuroscience (Neuroscience) Vol. 305 Pg. 1-14 (Oct 01 2015) ISSN: 1873-7544 [Electronic] United States
• PMID: 26232047 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Chemical References

• Lysosome-Associated Membrane Glycoproteins
• MicroRNAs
• RNA, Messenger

Topics

• Animals
• Brain (metabolism, pathology, ultrastructure)
• Brain Infarction (etiology)
• Brain Ischemia (complications)
• Disease Models, Animal
• Down-Regulation
• Gene Expression Profiling
• Laser-Doppler Flowmetry
• Lysosome-Associated Membrane Glycoproteins (metabolism)
• Male
• MicroRNAs (genetics, metabolism)
• Microscopy, Electron, Transmission
• Nervous System Diseases (etiology)
• RNA, Messenger (genetics, metabolism)
• Rats
• Rats, Sprague-Dawley
• Recovery of Function (physiology)
• Stroke (complications, etiology, pathology)