Targeting ASIC1a Promotes Neural Progenitor Cell Migration and Neurogenesis in Ischemic Stroke

作者全名："Ge, Hongfei; Zhou, Tengyuan; Zhang, Chao; Cun, Yupeng; Chen, Weixiang; Yang, Yang; Zhang, Qian; Li, Huanhuan; Zhong, Jun; Zhang, Xuyang; Feng, Hua; Hu, Rong"

作者地址："[Ge, Hongfei; Zhou, Tengyuan; Zhang, Chao; Chen, Weixiang; Yang, Yang; Li, Huanhuan; Zhong, Jun; Zhang, Xuyang; Feng, Hua; Hu, Rong] Third Mil Med Univ, Army Med Univ, Dept Neurosurg, Chongqing 400038, Peoples R China; [Ge, Hongfei; Zhou, Tengyuan; Zhang, Chao; Chen, Weixiang; Yang, Yang; Li, Huanhuan; Zhong, Jun; Zhang, Xuyang; Feng, Hua; Hu, Rong] Third Mil Med Univ, Army Med Univ, Southwest Hosp, Key Lab Neurotrauma, Chongqing 400038, Peoples R China; [Ge, Hongfei; Zhou, Tengyuan; Zhang, Chao; Zhang, Qian; Hu, Rong] Third Mil Med Univ, Army Med Univ, Southwest Hosp, Med Res Ctr, Chongqing 400038, Peoples R China; [Cun, Yupeng] Chongqing Med Univ, Pediat Res Inst, Natl Clin Res Ctr Child Hlth & Disorders, Minist Educ,Key Lab Child Dev & Disorders,Children, Chongqing 400014, Peoples R China"

通信作者："Feng, H; Hu, R (通讯作者)，Third Mil Med Univ, Army Med Univ, Dept Neurosurg, Chongqing 400038, Peoples R China.; Feng, H; Hu, R (通讯作者)，Third Mil Med Univ, Army Med Univ, Southwest Hosp, Key Lab Neurotrauma, Chongqing 400038, Peoples R China.; Hu, R (通讯作者)，Third Mil Med Univ, Army Med Univ, Southwest Hosp, Med Res Ctr, Chongqing 400038, Peoples R China."

来源：RESEARCH

ESI学科分类：　

WOS号：WOS:001012846000001

JCR分区：Q1

影响因子：8.5

年份：2023

卷号：6

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：　

摘要："Cell replacement therapy using neural progenitor cells (NPCs) has been shown to be an effective treatment for ischemic stroke. However, the therapeutic effect is unsatisfactory due to the imbalanced homeostasis of the local microenvironment after ischemia. Microenvironmental acidosis is a common imbalanced homeostasis in the penumbra and could activate acid-sensing ion channels 1a (ASIC1a), a subunit of proton-gated cation channels following ischemic stroke. However, the role of ASIC1a in NPCs post-ischemia remains elusive. Here, our results indicated that ASIC1a was expressed in NPCs with channel functionality, which could be activated by extracellular acidification. Further evidence revealed that ASIC1a activation inhibited NPC migration and neurogenesis through RhoA signaling-mediated reorganization of filopodia formation, which could be primarily reversed by pharmacological or genetic disruption of ASIC1a. In vivo data showed that the knockout of the ASIC1a gene facilitated NPC migration and neurogenesis in the penumbra to improve behavioral recovery after stroke. Subsequently, ASIC1a gain of function partially abrogated this effect. Moreover, the administration of ASIC1a antagonists (amiloride or Psalmotoxin 1) promoted functional recovery by enhancing NPC migration and neurogenesis. Together, these results demonstrate targeting ASIC1a is a novel strategy potentiating NPC migration toward penumbra to repair lesions following ischemic stroke and even for other neurological diseases with the presence of niche acidosis."

基金机构："National Natural Science Foundation of China [81873771, 81371340, 82271424]; Key Project of Natural Science Foundation of Chongqing [cstc2013jjB012503]"

基金资助正文："This project was supported by the National Natural Science Foundation of China (81873771, 81371340, and 82271424) and the Key Project of Natural Science Foundation of Chongqing (cstc2013jjB012503).& nbsp;"