Glycated albumin triggers fibrosis and apoptosis via an NADPH oxidase/Nox4-MAPK pathway-dependent mechanism in renal proximal tubular cells

In this study, we investigated the effects of GA on fibrosis and apoptosis of renal proximal tubular cells (NRK-52E) in vitro experiments. Our results showed that GA promoted α-SMA, fibronectin (FN) and TGF-β expressions in NRK-52E cells. GA also increased cell apoptosis and stimulated the expressions of pro-caspase 3/cleaved-caspase 3. GA overloading enhanced the phosphorylation of MAPK pathway. GA-induced α-SMA, FN, TGF-β and caspase 3 expressions were completely suppressed by the NADPH oxidase inhibitor apocynin (Apo), the reactive oxygen species (ROS) scavenger N-acetylcysteine (NAC) and the latent antioxidant Astragaloside IV (AS-IV). Real-time PCR showed that GA increased Nox1, Nox2 and Nox4 mRNA expressions, especially the Nox4 expression. Furthermore, Nox4 siRNA blocked GA-induced tubular damages and the MAPK pathway activation. These results demonstrate that GA increases the permissiveness of proximal tubular cells to fibrosis and apoptosis in vitro by triggering a pathway that involves NADPH oxidase/Nox4-MAPK signaling pathway. This event may represent a key cellular effect in increasing the susceptibility of tubular cells to fibrosis and apoptosis when the tubules cope with a high GA load. This effect is instrumental to renal damage and disease progression in patients with DN.
Source: Molecular and Cellular Endocrinology - Category: Endocrinology Source Type: research