Hypoxia-induced retinal pigment epithelium cell-derived bFGF promotes the migration and angiogenesis of HUVECs through regulating TGF-81/ smad2/3 pathway

Hypoxia promotes the secretion of basic fibroblast growth factor (bFGF) in retinal pigment epithelium (RPE), which plays an important part in retinopathy of prematurity (ROP). This study preliminarily explored the effect of hypoxia-induced RPE-derived bFGF on the biological functions of human umbilical vein endothelial cells (HUVECs). After cell culture in hypoxia conditions, the cell viability, apoptosis, and the expressions of bFGF and vascular endothelial growth factor A (VEGFA) in human RPEs were detected by 3-(4, 5-Dimethylthiazol-2-yl)2,5-diphenyltetrazolium bromide (MTT), flow cytometry, western blot, RT-qPCR, or ELISA. The HUVECs were transfected with siRNA for bFGF (sibFGF) or transforming growth factor-81 (TGF-81) (siTGF-81) and grown in the supernatant RPE under normoxia conditions or hypoxia conditions to further determine the cell viability, migration, angiogenesis, and the expressions of TGF-81, p-smad2/3, and smad2/3 in the cells by performing MTT, transwell, tube formation, Western blot, or RT-qPCR. Hypoxia culture decreased the cell viability and promoted the apoptosis as well as the expressions of bFGF and VEGFA in RPEs. In both normoxia and hypoxia conditions, RPE-derived bFGF increased the cell viability, migration, angiogenesis, and the expressions of TGF-81 and p-smad2/3 in the HUVECs, with hypoxia-induced RPE-derived bFGF showing a stronger effect than bFGF induced by normoxia. However, sibFGF reversed the effects caused by RPE-derived bFGF. Moreover, siTGF-81 decreased the high cell viability, migration and angiogenesis of HUVECs, and downregulated the expressions of TGF-81 and phosphorylated (p)-smad2/3 upregulated by hypoxia-induced RPE-derived bFGF. Hypoxia-induced RPE-derived bFGF could promote the migration and angiogenesis of HUVECs through regulating TGF-81/smad2/ 3 pathway.

Automated summary

Hypoxia promotes the secretion of bFGF in retinal pigment epithelium, playing a critical role in retinopathy of prematurity. The study found that hypoxia-induced RPE-derived bFGF can promote the migration and angiogenesis of HUVECs through regulating the TGF-81/smad2/3 pathway.