HOXA11-AS aggravates microglia-induced neuroinflammation after traumatic brain injury  

作　　者：Xiang-Long Li Bin Wang Fu-Bing Yang Li-Gang Chen Jian You 

机构地区：[1]Department of Neurosurgery,the Affiliated Hospital of Southwest Medical University,Luzhou,Sichuan Province,China [2]Neurosurgical Clinical Research Center and Academician(Expert)Workstation of Sichuan Province,Luzhou,Sichuan Province,China [3]Laboratory of Neurological Diseases and Brain Functions,the Affiliated Hospital of Southwest Medical University,Luzhou,Sichuan Province,China

出　　处：《Neural Regeneration Research》2022年第5期1096-1105,共10页中国神经再生研究（英文版）

基　　金：supported by the Science and Technology Project of Sichuan Province of China,No.2020YJ0188;the Science and Technology Foundation of Luzhou of China,No.2017LZXNYD-J10(both to XLL)。

摘　　要：Long noncoding RNAs(lnc RNAs)participate in many pathophysiological processes after traumatic brain injury by mediating neuroinflammation and apoptosis.Homeobox A11 antisense RNA(HOXA11-AS)is a member of the lnc RNA family that has been reported to participate in many inflammatory reactions;however,its role in traumatic brain injury remains unclear.In this study,we established rat models of traumatic brain injury using a weight-drop hitting device and injected LV-HOXA11-AS into the right lateral ventricle 2 weeks before modeling.The results revealed that overexpression of HOXA11-AS aggravated neurological deficits in traumatic brain injury rats,increased brain edema and apoptosis,promoted the secretion of proinflammatory factors interleukin-1β,interleukin-6,and tumor necrosis factorα,and promoted the activation of astrocytes and microglia.Microglia were treated with 100 ng/m L lipopolysaccharide for 24 hours to establish in vitro cell models,and then transfected with pc DNA-HOXA11-AS,mi R-124-3 p mimic,or sh-MDK.The results revealed that HOXA11-AS inhibited mi R-124-3 p expression and boosted MDK expression and TLR4-nuclear factor-κB pathway activation.Furthermore,lipopolysaccharide enhanced potent microglia-induced inflammatory responses in astrocytes.Forced overexpression of mi R-124-3 p or downregulating MDK repressed microglial activation and the inflammatory response of astrocytes.However,the mi R-124-3 p-mediated anti-inflammatory effects were reversed by HOXA11-AS.These findings suggest that HOXA11-AS can aggravate neuroinflammation after traumatic brain injury by modulating the mi R-124-3 p-MDK axis.This study was approved by the Animal Protection and Use Committee of Southwest Medical University(approval No.SMU-2019-042)on February 4,2019.

关 键 词：astrocyte competitive endogenous RNA HOXA11-AS MICROGLIA MIDKINE miR-124-3p NEUROINFLAMMATION traumatic brain injury 

分 类 号：R651.15[医药卫生—外科学]