Renal fibrosis is a progressive and chronic process that influences kidneys with chronic kidney disease (CKD), irrespective of cause, leading to irreversible failure of renal function and end-stage kidney disease. Among the signaling related to renal fibrosis, transforming growth factor-β1 (TGF-β1) signaling is a major pathway that induces the activation of myofibroblasts and the production of extracellular matrix (ECM) molecules. Apamin, a component of bee venom (BV), has been studied in relation to various diseases. However, the effect of apamin on renal interstitial fibrosis has not been investigated. The aim of this study was to estimate the beneficial effect of apamin in unilateral ureteral obstruction (UUO)-induced renal fibrosis and TGF-β1-induced renal fibroblast activation. This study revealed that obstructive kidney injury induced an inflammatory response, tubular atrophy, and ECM accumulation. However, apamin treatment suppressed the increased expression of fibrotic-related genes, including α-SMA, vimentin, and fibronectin. Administration of apamin also attenuated the renal tubular cells injury and tubular atrophy. In addition, apamin attenuated fibroblast activation, ECM synthesis, and inflammatory cytokines such as TNF-α, IL-1β, and IL-6 by suppressing the TGF-β1-canonical and non-canonical signaling pathways. This study showed that apamin inhibits UUO-induced renal fibrosis in vivo and TGF-β1-induced renal fibroblasts activation in vitro. Apamin inhibited the inflammatory response, tubular atrophy, ECM accumulation, fibroblast activation, and renal interstitial fibrosis through suppression of TGF-β1/Smad2/3 and STAT3 signaling pathways. These results suggest that apamin might be a potential therapeutic agent for renal fibrosis. KEY MESSAGES: UUO injury can induce renal dysfunction; however, apamin administration prevents renal failure in UUO mice. Apamin inhibited renal inflammatory response and ECM deposition in UUO-injured mice. Apamin suppressed the activation of myofibroblasts in vivo and in vitro. Apamin has the anti-fibrotic effect on renal fibrosis via regulation of TGF-β1 canonical and non-canonical signaling.
Keywords: Apamin; Myofibroblast; Renal fibrosis; STAT3; TGF-β1.
© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.