SIPA1 promotes angiogenesis by regulating VEGF secretion in Müller cells through STAT3 activation

作者全名："Fang, Yanhong; Wang, Qionghua; Zhang, Lanyue; Xie, Lin"

作者地址："[Fang, Yanhong; Xie, Lin] Chongqing Med Univ, Affiliated Hosp 3, Dept Ophthalmol, Chongqing, Peoples R China; [Fang, Yanhong; Wang, Qionghua; Zhang, Lanyue] Chongqing Univ, Jiangjin Hosp, Sch Med, Chongqing, Peoples R China"

通信作者："Xie, L (通讯作者)，Chongqing Med Univ, Affiliated Hosp 3, Dept Ophthalmol, Chongqing, Peoples R China."

来源：HELIYON

ESI学科分类：　

WOS号：WOS:001175099600001

JCR分区：Q2

影响因子：4

年份：2024

卷号：10

期号：2

开始页：　

结束页：　

文献类型：Article

关键词：SIPA1; Muller cells; VEGF; STAT3; Angiogenesis

摘要："Diabetic retinopathy (DR) is a prevalent complication of diabetes that can lead to vision loss. The chronic hyperglycemia associated with DR results in damage to the retinal microvasculature. Muller cells, as a kind of macroglia, play a crucial role in regulating the retinal vascular microenvironment. The objective of this study was to investigate the role of signal-induced proliferation-associated protein 1 (SIPA1) in regulating angiogenesis in Muller cells. Through proteomics, database analysis, endothelial cell function tests, and Western blot detection, we observed an upregulation of SIPA1 expression in Muller cells upon high glucose stimulation. SIPA1 expression contributed to VEGF secretion in Muller cells and regulated the mobility of retinal vascular endothelial cells. Further investigation of the dependence of SIPA1 on VEGF secretion revealed that SIPA1 activated the phosphorylation STAT3, leading to its translocation into the nucleus. Overexpression of SIPA1 combined with the STAT3 inhibitor STATTIC demonstrated the regulation of SIPA1 in VEGF expression, dependent on STAT3 activation. These findings suggest that SIPA1 promotes the secretion of pro-angiogenic factors in Muller cells by activating the STAT3 signaling pathway, thereby highlighting SIPA1 as a potential therapeutic target for DR."

基金机构："Natural Science Foundation of Chongqing, China CSTC [cstc2020jcyj-msxmX0698]; Chongqing Jiangjin District Science and Technology Bureau [Y2022017]; Leading project of Jiangjin Central Hospital affiliated to Chongqing University [2023LJXM004]"

基金资助正文："The study was supported by Natural Science Foundation of Chongqing, China CSTC (cstc2020jcyj-msxmX0698) , Chongqing Jiangjin District Science and Technology Bureau (Y2022017) and Leading project of Jiangjin Central Hospital affiliated to Chongqing University (2023LJXM004) ."