Novel small-molecule compound VCP979 attenuates renal fibrosis in male rats with unilateral ureteral obstruction

Abstract

Renal fibrosis is a hallmark of chronic kidney disease, while efficient therapy against renal fibrosis is still lacking. In this study, we investigated the role of a novel small-molecule compound VCP979 on renal fibrosis and inflammation in a rat model of unilateral ureteral obstruction (UUO). One week after the UUO surgery, rats were administered VCP979 by gavage for one week, and after treatment, magnetic resonance imaging of T1rho mapping and histopathological analysis were performed to evaluate renal fibrosis in vivo and ex vivo. This study showed that treatment with VCP979 effectively reduced renal fibrosis, extracellular matrix accumulation, and alleviated epithelial–mesenchymal transition in UUO rats, as well as improved renal function. In vivo T1rho mapping displayed increased T1rho values in the UUO rats, which was decreased after VCP979 treatment, and a positive correlation was detected between the T1rho values and the percentage of fibrotic area. Moreover, the administration of VCP979 also ameliorated the inflammatory cytokines expression and the infiltration of macrophages in renal tissues. Mechanistically, VCP979 treatment inhibited the activation of p38 mitogen–activated protein kinase, nuclear factor-kappa B, and transforming growth factor-β1/Smads signaling pathways. These results indicated that VCP979 could be an effective therapeutic agent for alleviating renal fibrosis and inflammation in the rat model of UUO via its antifibrotic and anti-inflammatory effects.