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

Abstract

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. Müller 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 Müller cells. Through proteomics, database analysis, endothelial cell function tests, and Western blot detection, we observed an up-regulation of SIPA1 expression in Müller cells upon high glucose stimulation. SIPA1 expression contributed to VEGF secretion in Müller 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 Müller cells by activating the STAT3 signaling pathway, thereby highlighting SIPA1 as a potential therapeutic target for DR.