Inhibition of the Rho/ROCK pathway promotes the expression of developmental and migration-related genes in astrocytes exposed to alcohol

作者全名："Qi, Xunzhong; Guo, Miao; Sun, Guangtao; Zhao, Huiying; Huang, Chenglong; Zhong, Xiaogang; Bai, Shunjie; Huang, Xinyan; Wu, Chengji; Huang, Zuoyi; Zhu, Xiaofeng"

作者地址："[Qi, Xunzhong; Sun, Guangtao; Wu, Chengji; Huang, Zuoyi] Jiamusi Univ, Affiliated Hosp 1, Dept Neurol, Jiamusi, Peoples R China; [Huang, Xinyan] Jiamusi Univ, Affiliated Hosp 2, Jiamusi, Peoples R China; [Guo, Miao] Jiamusi Univ, Jiamusi, Peoples R China; [Zhao, Huiying] Yichun Forestry Adm Cent Hosp, Dept Neurol, Yichun, Peoples R China; [Zhong, Xiaogang] Chongqing Med Univ, Affiliated Hosp 1, Chongqing, Peoples R China; [Zhong, Xiaogang] Chongqing Med Univ, Coll Basic Med, Chongqing, Peoples R China; [Bai, Shunjie] Chongqing Med Univ, Affiliated Hosp 1, Chongqing, Peoples R China; [Huang, Chenglong] Chongqing Med Univ, Dept Clin Lab, Univ Town Hosp, Chongqing, Peoples R China; [Zhu, Xiaofeng] Mudanjiang Med Coll, Mudanjiang 157012, Peoples R China; [Zhu, Xiaofeng] 48 Dexiang St, Jiamusi 154002, Heilongjiang, Peoples R China"

通信作者："Zhu, XF (通讯作者)，48 Dexiang St, Jiamusi 154002, Heilongjiang, Peoples R China."

来源：ALCOHOL

ESI学科分类：NEUROSCIENCE & BEHAVIOR

WOS号：WOS:001167050500001

JCR分区：Q2

影响因子：2.3

年份：2024

卷号：115

期号：　

开始页：5

结束页：12

文献类型：Article

关键词：Alcohol dependence; Astrocyte; Rho/ROCK pathway; Transcriptome sequencing

摘要："Astrocytes are an important regulator of alcohol dependence. Furthermore, the downregulation of Rho-associated coiled coil-containing protein kinase 2 (ROCK2) attenuates alcohol-induced inflammation and oxidative stress in astrocytes. On the basis of these findings, we examined the effects of alcohol and a Rho/RACK kinases inhibitor on astrocyte function and investigated their effects on mRNA expression to further explore the protective mechanisms of a Rho/RACK kinases inhibitor in astrocytes after alcohol exposure. CTX TNA2 astrocytes were cultured with alcohol and Rho/RACK kinases inhibitor intervention before undergoing transcriptome sequencing, quantitative reverse transcription polymerase chain reaction (qRT-PCR), and wound healing assays. Alcohol exposure modulated cell morphology and inhibited astrocyte migration, whereas Fasudil improved cell morphology and promoted astrocyte migration after alcohol exposure. Transcriptome sequencing results indicated that alcohol exposure modulates the expression of genes involved in astrocyte development. Fasudil reversed the effects of alcohol exposure on the astrocyte developmental process. Four genes related to the developmental process and migration - Ccl2, Postn, Itga8, and Serpine1 - with the highest protein-protein interaction correlations (node degree >7) were selected for verification by qRT-PCR, and the results were consistent with those of the sequencing and wound healing assays. Our results suggest that the Rho/ROCK pathway is essential for alcohol to be able to interfere with astrocyte development and migration gene expression. The Rho/ROCK pathway inhibitor Fasudil reversed the adverse effects of alcohol exposure on astrocytes and may have clinical applications."

基金机构："Doctoral Initiation Project of Jiamusi University [JMSUBZ2019-06]; Talent training project for basic scientific research of Heilongjiang Province Educational Commission of China [2019- KYYWF-1357]; National Key R &D Program of China [2018YFC1314404]; National Natural Science Foundation of China [81901398]; Natural Science Foundation of Chongqing, China [cstc2019jcyj-msxmX0 025]"

基金资助正文："This work was supported by the Doctoral Initiation Project of Jiamusi University (Grant numbers: JMSUBZ2019-06) ; Talent training project for basic scientific research of Heilongjiang Province Educational Commission of China (Grant numbers: 2019- KYYWF-1357) : The National Key R &D Program of China (Grant numbers: 2018YFC1314404) ; National Natural Science Foundation of China (Grant numbers: 81901398) ; Natural Science Foundation of Chongqing, China (Grant numbers: cstc2019jcyj-msxmX0 025) ."