Sortilin inhibition in microglial cells cannot alleviate ischemia and hypoxia-induced neuronal injury in co-culture

作者全名：Long, Shuang; Liu, Zhao; Wang, Yan

作者地址：[Long, Shuang; Wang, Yan] Chongqing Med Univ, Inst Neurosci, Sch Basic Med Sci, Chongqing 400016, Peoples R China; [Liu, Zhao] Chongqing Gen Hosp, Dept Neurol, Chongqing, Peoples R China

通信作者：Wang, Y (通讯作者)，Chongqing Med Univ, Inst Neurosci, Sch Basic Med Sci, Chongqing 400016, Peoples R China.

来源：NEUROREPORT

ESI学科分类：NEUROSCIENCE & BEHAVIOR

WOS号：WOS:001233704200002

JCR分区：Q4

影响因子：1.6

年份：2024

卷号：35

期号：5

开始页：320

结束页：327

文献类型：Article

关键词：hypoxia-ischemia; microglial cells; PGRN; sortilin

摘要：Sortilin is a single-pass type I transmembrane protein which can bind to various cargo proteins, regulating their surface location, secretion, or degradation in lysosomes. In our previous study, we found that sortilin can regulate progranulin expression by transporting it to lysosomes and reduce neuronal cell injury in hypoxia-ischemia, but the expression and function of sortilin in microglial cells during hypoxia-ischemia are unknown. The purpose of this study was to further investigate the function of sortilin in microglial cells and its effect on neuron cells. In rat BV2 microglial cells, sortilin was knocked down by lentivirus. After oxygen-glucose deprivation/reperfusion (OGD/R), expression of sortilin, progranulin (PGRN) and JNK pathway was detected by western blot, immunofluorescence was used to show the localization of PGRN, secretion of TNF alpha/IL-6 was measured by Elisa. Then co-culture microglial cells with neuron cells during hypoxia-ischemia and detected the neuron injury by CCK-8 and TUNEL. The expression of sortilin, mature and cleaved PGRN were all increased after OGD/R in microglial cells. Furthermore, sortilin inhibition accompany with less PGRN localization in lysosomes and more mature and less cleaved PGRN expression in microglial cells. Sortilin inhibition also can reduce the inflammatory response in microglial cells, but it does not alleviate neuronal injury in co-culture. This study demonstrated that sortilin can regulate the expression of PGRN and reduce the inflammatory response in microglial cells. However, only inhibiting sortilin in microglial cells did not have an impact on the survival of neurons during ischemia-hypoxia

基金机构：National Natural Science Foundation of China [81801506]; Chongqing Natural Science Foundation [CSTB2022NSCQ-MSX1457]

基金资助正文：We thank LetPub (www.letpub.com) for its linguistic assistance during the preparation of this manuscript. This study was supported by the National Natural Science Foundation of China (81801506) and Chongqing Natural Science Foundation (No. CSTB2022NSCQ-MSX1457).Conception and design: Shuang Long, Yan Wang. Experiments: Shuang Long, Yan Wang. Data analysis and interpretation: Shuang Long, Yan Wang, Zhao Liu. Writing-original draft: Yan Wang. Writing-review and editing: Shuang Long, Yan Wang, Zhao Liu. Funding acquisition: Yan Wang.