Apelin reduced glomerular matrix deposition from 14.60% to 10.76% and alleviated basement membrane thickening in diabetic mice via the endothelial APJ-activated SIRT3-KLF15 pathway.
Apelin/APJ signaling reduces glomerular basement membrane thickening in diabetic nephropathy by preventing laminin and collagen IV synthesis via the SIRT3-KLF15 pathway in glomerular endothelial cells.
Absolute Event Rate: 10.76% vs 14.6%
p-value: p=<0.001
Glomerular basement membrane (GBM) thickening, the earliest morphological change of diabetic nephropathy (DN), is related to glomerular endothelial cells (GECs) dysfunction which increase extracellular matrix (ECM) synthesizing. Apelin, the endogenous ligand for apelin/apelin receptor (APJ), is reported to alleviate endothelial cell dysfunction in DN. Therefore, it was hypothesized that apelin/APJ reduced GBM thickening by decreasing the synthesis of ECM in GECs. The results showed that apelin reduced glomerular fibrosis and GBM thickening by decreasing the expression of laminin and collagen IV in diabetic mice, which were cancelled following APJ knockout in GECs. Furthermore, apelin/APJ inhibited the synthesis of laminin and collagen IV in GECs by increasing the expression and activity of SIRT3, which promoted KLF15 deacetylation and translocation into nucleus. In conclusion, apelin/APJ reduced GBM thickening in diabetes mellitus by preventing laminin and collagen IV synthesizing via SIRT3‑KLF15 pathway in GECs.
Huang et al. (Fri,) conducted a other in Diabetic nephropathy (n=48). Apelin-13 vs. Streptozotocin (STZ) alone was evaluated on Glomerular matrix deposition (PAS staining positive area) (p=<0.001). Apelin reduced glomerular matrix deposition from 14.60% to 10.76% and alleviated basement membrane thickening in diabetic mice via the endothelial APJ-activated SIRT3-KLF15 pathway.