title: MicroRNA-30b promotes axon outgrowth of retinal ganglion cells by inhibiting Semaphorin3A expression.
abstract: Semaphorin3A (Sema3A) is a major inhibitory factor of optic nerve (ON) regeneration post-injury. Many microRNAs (miRNAs) are expressed specifically in the mammalian brain and retina and are dynamically regulated during development, suggesting that this group of miRNAs may be associated with neural development. We found that microRNA-30b (miR-30b) bound to the three prime untranslated region (3' UTR) of Sema3A and inhibited the expression of Sema3A mRNA. The mRNA expression level of miR-30b and the protein expression levels of Sema3A, Neuropilin1 (NRP1), PlexinA1 (PlexA1), phosphorylated p38MAPK (p-p38MAPK), and active caspase-3 were all upregulated in retinas from rats with a damaged ON relative to those with an intact ON. Transfection of cultured retinal ganglion cells (RGCs) with an miR-30b mimic led to decreased levels of Sema3A, NRP1, PlexA1, p-p38MAPK, and active caspase-3 protein expression, as well as axon elongation and reduced levels of apoptosis. These findings provide evidence that miR-30b inhibits Sema3A expression. Decreased Sema3A expression promotes axon outgrowth in RGCs due to reduced levels of Sema3A binding to NRP1 and PlexA1 and simultaneously reduces apoptosis by inhibiting the p38MAPK and caspase-3 pathways. Our findings provide the first evidence that miR-30b-mediated Sema3A downregulation may serve as a new strategy for the clinical treatment of ON injury.
authors: Department of Ophthalmology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, China.
authors: F
authors: F
authors: Han
authors: Department of Ophthalmology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, China.
authors: Y
authors: Y
authors: Huo
authors: Department of Ophthalmology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, China.
authors: C-J
authors: CJ
authors: Huang
authors: Department of Ophthalmology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, China.
authors: C-L
authors: CL
authors: Chen
authors: Department of Ophthalmology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, China. Electronic address: yejian1979@126.com.
authors: J
authors: J
authors: Ye
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D001369:Axons; D053148:Caspase 3 / Q000378:metabolism; D005260:Female; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D009416:Nerve Regeneration; D039942:Neuropilin-1 / Q000378:metabolism; D020221:Optic Nerve Injuries / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012165:Retinal Ganglion Cells / Q000378:metabolism*; D040121:Semaphorin-3A / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: C556157:MIRN30 microRNA, rat; D035683:MicroRNAs; C488218:Sema3a protein, rat; D040121:Semaphorin-3A; D039942:Neuropilin-1; D048051:p38 Mitogen-Activated Protein Kinases; D053148:Caspase 3
keywords: RGCs; Regeneration; Sema3A; miR-30b