The mechanism of attenuation of epithelial-mesenchymal transition by a phosphodiesterase 5 inhibitor via renal klotho expression

Abstract

Phosphodiesterase-5 (PDE-5) inhibitors induces vasodilation in several organs by blocking cyclic GMP (guanosine monophosphate) degradation. However, the existence of alternative mechanism of action in case of an impaired nitric oxide (NO) system remains controversial. Previous studies suggested that decreased NO bioavailability may result in the downregulation of klotho expression, but the relationship between klotho and NO remains obscure. Therefore, we investigated whether a PDE-5 inhibitor could preserve epithelial–mesenchymal transition (EMT) and relationship exists between the NO and renal klotho expression. Ten-week-old SD rats (N = 24, 200 g, male) were divided (N = 6) into four groups, which received: A LSD, L-NAME 1 mg/mL in drinking water, Udenafil 5 mg/kg subcutaneously and both for 4 weeks. Urine nitrate/nitrite, NGAL (Neutrophil gelatinase-associated lipocalin), and cGMP were measured using ELISA. Kidney was subjected to evaluate PCNA (proliferative cell nuclear antigen), α-SMA (smooth muscle cell antigen), E-cadherin, and klotho expression. Urine cGMP decreased after treatment of PDE-5 inhibitor compared with control due to blocking degradation of cGMP (P