title: 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.affiliation: College of Rehabilitation Medicine & TCM Rehabilitation Research Center Of SATCM, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, PR China.
authors.forename: J
authors.initials: J
authors.lastname: Tao
authors.affiliation: College of Rehabilitation Medicine & TCM Rehabilitation Research Center Of SATCM, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, PR China.
authors.forename: W
authors.initials: W
authors.lastname: Liu
authors.affiliation: Fujian Rehabilitation Tech Co-innovation Center (2011 Project), Fujian University of Traditional Chinese Medicine, Fuzhou 350122, PR China.
authors.forename: G
authors.initials: G
authors.lastname: Shang
authors.affiliation: Fujian Rehabilitation Tech Co-innovation Center (2011 Project), Fujian University of Traditional Chinese Medicine, Fuzhou 350122, PR China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Fujian Rehabilitation Engineering Research Center & Fujian Key Lab of Motor Function Rehabilitation, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, PR China.
authors.forename: J
authors.initials: J
authors.lastname: Huang
authors.affiliation: Fujian Rehabilitation Tech Co-innovation Center (2011 Project), Fujian University of Traditional Chinese Medicine, Fuzhou 350122, PR China.
authors.forename: R
authors.initials: R
authors.lastname: Lin
authors.affiliation: College of Rehabilitation Medicine & TCM Rehabilitation Research Center Of SATCM, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, PR China. Electronic address: fjtcm1958@sina.com.
authors.forename: L
authors.initials: L
authors.lastname: Chen
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D020520:Brain Infarction / Q000209:etiology; D002545:Brain Ischemia / Q000150:complications; D004195:Disease Models, Animal; D015536:Down-Regulation; D020869:Gene Expression Profiling; D017078:Laser-Doppler Flowmetry; D051907:Lysosomal Membrane Proteins / Q000378:metabolism*; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D046529:Microscopy, Electron, Transmission; D009422:Nervous System Diseases / Q000209:etiology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000502:physiology*; D020521:Stroke / Q000150:complications / Q000209:etiology / Q000473:pathology*
chemical_list: D051907:Lysosomal Membrane Proteins; D035683:MicroRNAs; D012333:RNA, Messenger
keywords: autophagy; lysosome; miR-207; miR-352; stroke