Angiogenesis, increased glomerular permeability, and
albuminuria are thought to contribute to the progression of
diabetic nephropathy (DN).
Apelin receptor (
APLNR) and the endogenous
ligand of
APLNR,
apelin, induce the sprouting of endothelial cells in an autocrine or paracrine manner, which may be one of the mechanisms of DN. The aim of this study was to investigate the role of
apelin in the pathogenesis of DN. Therefore, we observed
apelin/
APLNR expression in kidneys from patients with
type 2 diabetes as well as the correlation between
albuminuria and serum
apelin in patients with
type 2 diabetes. We also measured the proliferating, migrating, and chemotactic effects of
apelin on glomerular endothelial cells. To measure the permeability of
apelin in glomerular endothelial cells, we used transwells to detect
FITC-BSA penetration through monolayered glomerular endothelial cells. The results showed that serum
apelin was significantly higher in the patients with
type 2 diabetes compared to healthy people (p<0.05, Fig. 1B) and that urinary
albumin was positively correlated with serum
apelin (R = 0.78, p<0.05).
Apelin enhanced the migration, proliferation, and chemotaxis of glomerular endothelial cells in a dose-dependent manner (p<0.05).
Apelin also promoted the permeability of glomerular endothelial cells (p<0.05) and upregulated the expression of VEGFR2 and Tie2 in glomerular endothelial cells (p<0.05). These results indicated that upregulated
apelin in
type 2 diabetes, which may be attributed to increased fat mass, promotes angiogenesis in glomeruli to form abnormal vessels and that enhanced
apelin increases permeability via upregulating the expression of VEGFR2 and Tie2 in glomerular endothelial cells.