LGALS3BP in Microglia Promotes Retinal Angiogenesis Through PI3K/AKT Pathway During Hypoxia

作者全名："Zhao, Chenyang; Liu, Yusen; Meng, Jiayu; Wang, Xiaotang; Liu, Xianyang; Li, Wanqian; Zhou, Qian; Xiang, Junjie; Li, Na; Hou, Shengping"

作者地址："[Zhao, Chenyang; Liu, Yusen; Meng, Jiayu; Wang, Xiaotang; Liu, Xianyang; Li, Wanqian; Zhou, Qian; Xiang, Junjie; Hou, Shengping] Chongqing Med Univ, Affiliated Hosp 1, Chongqing, Peoples R China; [Zhao, Chenyang; Liu, Yusen; Meng, Jiayu; Wang, Xiaotang; Li, Wanqian; Zhou, Qian; Xiang, Junjie; Hou, Shengping] Chongqing Key Lab Ophthalmol, Chongqing, Peoples R China; [Zhao, Chenyang; Liu, Yusen; Meng, Jiayu; Wang, Xiaotang; Liu, Xianyang; Li, Wanqian; Zhou, Qian; Xiang, Junjie; Hou, Shengping] Natl Clin Res Ctr Ocular Dis, Chongqing Branch, Chongqing, Peoples R China; [Li, Na] Chongqing Med Univ, Coll Basic Med, Chongqing, Peoples R China; [Hou, Shengping] Chongqing Med Univ, Affiliated Hosp 1, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China; [Li, Na] Chongqing Med Univ, Coll Basic Med, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China"

通信作者："Hou, SP (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China.; Li, N (通讯作者)，Chongqing Med Univ, Coll Basic Med, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China."

来源：INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:000865420100002

JCR分区：Q1

影响因子：4.4

年份：2022

卷号：63

期号：8

开始页：　

结束页：　

文献类型：Article

关键词：LGALS3BP; microglia; angiogenesis; angiogenic factors

摘要："PURPOSE. Retinal microglia promote angiogenesis and vasculopathy in oxygen-induced retinopathy (OIR); however, its specific molecular mechanism in the formation of retinal angiogenesis remains unclear. The lectin galactoside-binding soluble 3 binding protein (LGALS3BP), a member of the scavenger receptor cysteine-rich (SRCR) domain protein family, is involved in tumor neovascularization, and we therefore hypothesized that LGALS3BP plays an active role in microglia-induced angiogenesis. METHODS. The expression of LGALS3BP in microglia was detected by immunofluorescence, RT-qPCR, and western blotting. Functional assays of human umbilical vein endothelial cells (HUVECs) such as migration, proliferation, and tube formation were measured by Transwell, EdU, and Matrigel assays. Angiogenesis-related factors and PI3K/AKT levels were detected by western blotting. The relationship between LGALS3BP and PI3K or HIF-1 alpha was investigated by immunoprecipitation. RESULTS. Our results showed that the expression of LGALS3BP was significantly increased in microglia surrounding neovascularization of the OIR mice and was also upregulated in human microglial clone 3 (HMC3) cells after hypoxia. Moreover, HUVECs co-cultured with hypoxic HMC3 cells showed increased migration, proliferation, and tube formation, as well as levels of angiogenesis-related factor. However, the proangiogenic ability and angiogenesis-related factor expression of HMC3 cells was suppressed after silencing LGALS3BP. LGALS3BP induces the upregulation of angiogenesis-related factors through the PI3K/AKT pathway and then promotes angiogenesis in microglia. CONCLUSIONS. Collectively, our findings suggest that LGALS3BP in microglia plays an important role in angiogenesis, suggesting a potential therapeutic target of LGALS3BP for angiogenesis."

基金机构："National Natural Science Foundation Project of China [81873678, 82070951]; Natural Science Foundation Project of Chongqing [cstc2019jcyjmsxmX0120]; Innovation Supporting Plan of Overseas Study of Chongqing [cx2018010]; Innovative Research Group Project of Chongqing Education Commission [CXQT19015]; Chongqing Education Commission [KJQN202000406]; National Key Clinical Specialties Construction Program of China, Chongqing Branch of National Clinical Research Center for Ocular Diseases, Chongqing Key Laboratory of Ophthalmology [2008CA5003]; Natural Science Foundation Project of Chongqing Medical University [W0047]"

基金资助正文："Supported by grants from the National Natural Science Foundation Project of China (81873678, 82070951) , Natural Science Foundation Project of Chongqing (cstc2019jcyjmsxmX0120) , Innovation Supporting Plan of Overseas Study of Chongqing (cx2018010) , Innovative Research Group Project of Chongqing Education Commission (CXQT19015) , Chongqing Education Commission (KJQN202000406) , National Key Clinical Special- ties Construction Program of China, Chongqing Branch of National Clinical Research Center for Ocular Diseases, Chongqing Key Laboratory of Ophthalmology (2008CA5003) , and Natural Science Foundation Project of Chongqing Medical University (W0047) ."