The Effect of Angiotensin IV on Plasminogen Activator Inhibitor-1 Expression in Rat Mesangial Cells Cultured in High Glucose

Angiotensin II (Ang II) contributes to the development of diabetic glomerulosclerosis by increasing glomerular plasminogen activator inhibitor-1 (PAI-1) expression. Biological activities of angiotensin IV (Ang IV), the Ang degradation product, on renal cells and association between Ang IV and diabetic nephropathy are unclear. We aimed to elucidate effects of Ang IV on PAI-1 expression in rat mesangial cells (RMCs) cultured in high glucose. Primary cultures of RMCs were obtained from isolated, collagenase-treated rat glomeruli. Effects of Ang II/IV and high ambient glucose on PAI-1 antigen and mRNA in RMCs were examined. Inhibitory effects of angiotensin type 1, 2, and 4 receptor antagonists on Ang II- and IV-mediated PAI-1 expression were also determined. PAI-1 antigen and mRNA were measured by enzyme-linked immunosorbent assay and reverse transcriptase-polymerase chain reaction, respectively. Ang IV significantly increased both protein and mRNA levels of PAI-1 in RMCs cultured in normal and high glucose conditions. Ang IV-induced increased PAI-1 protein and mRNA were completely attenuated by coculturing with AT4 receptor antagonist, but not with ATI or AT2 receptor antagonist. These data suggest that Ang IV may be implicated in the pathogenesis of diabetic nephropathy through increasing mesangial cell PAI-1 expression