CLK2-SOX3 combination promotes choroidal neovascularization by SGLT1 inducing endothelial cell metabolic reprogramming.

Choroidal neovascularization (CNV) is one of the main causes of visual loss. Endothelial cell metabolic reprogramming is an important mechanism in regulating pathological neovascularization. However, how endothelial cell metabolic reprogramming is regulated in CNV is not yet clear. In this study, we constructed CNV mouse model by laser injury and in vitro cell model by hypoxia-induced mouse brain microvascular endothelial cells (BMECs). We identified glucose transporter Sodium-Dependent Glucose Transporter 1 (SGLT1) regulating endothelial cell metabolic reprogramming by siRNA transfection and metabolomics analysis. Mechanistically, we manifested the TCTTTGTCTG and ATTGCCTC sequences in the sglt1 promoter was targeted by SRY-box transcription factor 3 (SOX3). Furtherly, the function of SOX3 was induced by its Ser97 site combining with CDC-like kinase 2 (CLK2). Our results show that the CLK2-SOX3 combination targets sglt1, thereby inducing metabolic reprogramming of endothelial cells and promoting CNV.