miR-126 promotes angiogenesis and attenuates inflammation after contusion spinal cord injury in rats.
MicroRNAs are a class of small RNAs that regulate the expression of target mRNAs by inhibiting translation or destabilizing target mRNAs. miR-126 is a microRNA that is highly enriched in endothelial cells. miR-126 has been found to promote angiogenesis and inhibit vascular inflammation in endothelial cells by repressing three target genes Sprouty-related EVH1 domain-containing protein 1 (SPRED1), phosphoinositol-3 kinase regulatory subunit 2 (PIK3R2), and vascular cell adhesion molecule 1 (VCAM1). Our previous study showed that the expression of miR-126 was downregulated after spinal cord injury (SCI). Therefore, we wanted to examine whether upregulation of miR-126 could promote angiogenesis, inhibit inflammation, and exert a positive effect on recovery after contusion SCI. In this study, we found that increased levels of miR-126 promoted angiogenesis, and inhibited leukocyte extravasation into the injured spinal cord, which was concurrent with downregulation of mRNA and protein expression of three validated miR-126 target genes, SPRED1, PIK3R2, and VCAM1. Moreover, a dose-dependent effect of miR-126 was observed in rescuing tissue damage and improving the functional deficit after SCI. Thus, the present study indicated that miR-126 played an important role in angiogenesis and inflammation after SCI.
Department of Spine Surgery, Xiangya Hospital, Central South University, Changsha 410008, PR China.
Jianzhong
J
Hu
Department of Spine Surgery, Xiangya Hospital, Central South University, Changsha 410008, PR China.
Lei
L
Zeng
Department of Spine Surgery, Xiangya Hospital, Central South University, Changsha 410008, PR China.
Jianghu
J
Huang
Department of Spine Surgery, Xiangya Hospital, Central South University, Changsha 410008, PR China.
Guan
G
Wang
Department of Sports Medicine, Research Center of Sports Medicine, Xiangya Hospital, Central South University, Changsha 410008, PR China. Electronic address: hongbinlu@hotmail.com.
Hongbin
H
Lu
D000818:Animals; D044842:Cullin Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects*; D007249:Inflammation / Q000188:drug therapy* / Q000209:etiology; D017493:Leukocyte Common Antigens / Q000378:metabolism; D007962:Leukocytes / Q000187:drug effects / Q000473:pathology; D008124:Locomotion / Q000187:drug effects; D008297:Male; D035683:MicroRNAs / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000209:etiology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D012330:RNA, Double-Stranded / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017483:Receptors, Vasopressin / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D013119:Spinal Cord Injuries / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D013997:Time Factors; D066127:White Matter / Q000473:pathology
C094547:Cul5 protein, rat; D044842:Cullin Proteins; C571458:MIRN126 microRNA, rat; D035683:MicroRNAs; D012330:RNA, Double-Stranded; D017483:Receptors, Vasopressin; D012097:Repressor Proteins; C499021:Spred1 protein, rat; D019869:Phosphatidylinositol 3-Kinases; D017493:Leukocyte Common Antigens
Angiogenesis; Inflammation; Spinal cord injury; miR-126; microRNA