The SGLT2 Inhibitors Empagliflozin Alleviate Renal Fibrosis by Inhibiting CTGF-Mediated Epithelial-Mesenchymal Transition in Diabetic Sprague-Dawley (SD) Rats

Objective: Aims to investigate the effects of empagliflozin (EMPA), a sodium-glucose co-transporter 2 (SGLT2) inhibitor, on renal fibrosis in male diabetic Sprague-Dawley (SD) rat model. Methods: Streptozotocin(STZ) were injected to establish diabetes model, EMPA (10 mg/kgd) or normal saline (NS) were administered for four weeks. The changes in renal fibrosis-related biomarkers, include vimentin (VIM), collagen types I(Col-I), collagen types III(Col-III), fibroblast-specific protein 1(FSP-1), connective tissue growth factor (CTGF), fibronectin (FN) were evaluated. Renal pathology, serum glucose levels and urinary protein excretion were also assessed. Results: Biomarkers of renal fibrosis were significantly reduced in the EMPA group compared to those in the NS group after 4-week treatment, including VIM (519.8483.37 vs. 663.2791.84 ng/ml, P0.05), Col-I (21.271.46 vs. 25.712.82 ng/ml , P0.05) and Col-III (7.061.12 vs. 9.431.36 ng/ml, P0.05), FSP-1 (4.380.81 vs. 5.700.78 ng/ml, P0.05), and CTGF (1147217 vs. 1556235 pg/ml, P0.05),respectively. Nevertheless, compared to normal control (NC) group, the levels of renal fibrosis-related biomarkers in the EMPA group showed no significant differences except for VIM, which was VIM (336.6628.87 vs. 519.8483.37 ng/mL, P0.001). NS group rats showed notable renal tubular dilation and casts, EMPA group exhibited only mild tubular dilation. Conclusion: These findings suggest that empagliflozin reverse renal fibrosis potentially through inhibiting CTGF-mediated epithelial-mesenchymal transition.