Preprint Article Version 2 Preserved in Portico This version is not peer-reviewed

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

Version 1 : Received: 21 February 2024 / Approved: 22 February 2024 / Online: 22 February 2024 (15:24:51 CET)
Version 2 : Received: 23 February 2024 / Approved: 23 February 2024 / Online: 23 February 2024 (13:25:01 CET)

How to cite: Ji, K.; Zeng, X.; Wei, J.; Zhang, L.; Hao, L.; Fan, M.; Chen, X. The SGLT2 Inhibitors Empagliflozin Alleviate Renal Fibrosis by Inhibiting CTGF-Mediated Epithelial-Mesenchymal Transition in Diabetic Sprague-Dawley (SD) Rats. Preprints 2024, 2024021288. https://doi.org/10.20944/preprints202402.1288.v2 Ji, K.; Zeng, X.; Wei, J.; Zhang, L.; Hao, L.; Fan, M.; Chen, X. The SGLT2 Inhibitors Empagliflozin Alleviate Renal Fibrosis by Inhibiting CTGF-Mediated Epithelial-Mesenchymal Transition in Diabetic Sprague-Dawley (SD) Rats. Preprints 2024, 2024021288. https://doi.org/10.20944/preprints202402.1288.v2

Abstract

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/kg·d) 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 (519.84±83.37 vs. 663.27±91.84 ng/ml, P<0.05), Col-I (21.27±1.46 vs. 25.71±2.82 ng/ml , P<0.05) and Col-III (7.06±1.12 vs. 9.43±1.36 ng/ml, P<0.05), FSP-1 (4.38±0.81 vs. 5.70±0.78 ng/ml, P<0.05), and CTGF (1147±217 vs. 1556±235 pg/ml, P<0.05),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 (336.66±28.87 vs. 519.84±83.37 ng/mL, P<0.001). 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.

Keywords

SGLT2 Inhibitors; Empagliflozin; Renal fibrosis; Connective tissue growth factor; Epithelial-mesenchymal transition

Subject

Medicine and Pharmacology, Endocrinology and Metabolism

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