Catalpol prevents glomerular angiogenesis induced by advanced glycation end products via inhibiting Galectin-3

Abstract

Objectives: The main characteristics of Diabetic Nephropathy (DN) at the early stage is abnormal angiogenesis of glomerular endothelial cells and macrophage infiltration. Galectin-3 plays a pivotal role in the pathogenesis of DN via binding with its ligand, Advanced Glycation End products (AGEs). Catalpol (Cat.), an iridoid glucoside extracted fromRehmannia glutinosa, has been found to ameliorate vascular inflammation, reduce endothelial permeability and protect endothelial damage upon diabetic milieu. However, little is known about whether Cat. could exert anti-angiogenesis and anti-inflammation effect induced by AGEs. Methods:The anti-angiogenic mechanisms of Cat. were examined by incubating mouse glomerular endothelial cells (mGECs) and RAW 264.7 macrophages induced by AGEs. The expression of Galectin-3 and correlated molecules were also detected in diabetic rats treated with Cat.Key findings: We observed that Galectin-3/Hypoxia-inducible factor-1(HIF-1α)was activated by AGEs in mGECs and RAW 264.7 macrophages, catalpol significantly inhibited the proliferation of the mGECs and RAW 264.7 macrophages in vitro.Meanwhile, it also ameliorateddiabetes-induced renal damage via inhibiting Galectin-3/VEGF/HIF-1α pathways in vivo.Conclusions: Altogether, our findings demonstrated that Cat. prevent the angiogenesis of mGECs and macrophages proliferation via inhibiting Galectin-3. We suggest that Cat.contributes to block the pathogenic development of diabetes-induced renal damage.