Renoprotective Effects of Empagliflozin Against Experimentally Induced Renal Fibrosis In Vitro

Abstract

ID 21668 Poster Board 454 Background: Chronic kidney disease (CKD) is a progressive disease characterized by gradual loss of kidney function over time. Diabetes, hypertension, and obesity are the leading risk factors for developing CKD. Fibrosis is regarded as the final common pathway leading to CKD due to the irreversible damage it causes to the nephrons. Sodium-glucose co-transporter 2 (SGLT-2) inhibitors (Dapagliflozin and Canagliflozin) have been shown to be renoprotective in type 2 diabetes patients. However, the renoprotective mechanisms of the SGLT-2 inhibitors are unclear. Our study investigated whether empagliflozin (an SGLT-2 inhibitor) treatment inhibits fibrosis induced by transforming growth factor-b (TGF-b) and profibrotic signaling in rat renal proximal tubular cells (NRK-52E).Methods: NRK-52E cells were cultured and treated with TGF-b with or without empagliflozin for 48 hours. The expression of fibrosis marker -vimentin, autophagy marker -LC3II, and TGF-b-mediated profibrotic signaling marker -SMAD 2were measured by western blotting.Results: TGF-b treatment (at 5 ng/mL) for 48 hours induced fibrosis and activated autophagy signaling in renal proximal tubular cells. Specifically, 48 h TGF-b treatment at 5 ng/mL induced the expression of Vimentin by 1.57-fold and LC3II by 2.6-fold and increased the phosphorylation of SMAD 2 by 3.49-fold compared to vehicle-treated cells. Co-treatment with empagliflozin (100 and 500 nM) reduced the expression of the fibrotic markers (vimentin), autophagy marker (LC3II), and TGF-b-mediated phosphorylation of SMAD-2 in renal proximal tubular cells. Conclusions:Our findings indicate that TGF-b-mediated induction of fibrosis, autophagy, and profibrotic signaling in renal proximal tubular cells could be attenuated by empagliflozin treatment. Further studies are required to understand the molecular mechanisms that underpin the antifibrotic effects of empagliflozin against TGF-b-induced renal fibrosis.