Endocrine Abstracts

Aim: Fibroblast growth factor 21, a well-known regulator of metabolic disorders, exhibits the potential to prevent renal fibrosis by negatively regulating the transforming growth factor β (TGF-β)/Smad3 signaling pathway. Gemigliptin and dipeptidyl peptidase-4 inhibitors are frequently utilized in the management of patients with type 2 diabetes. However, the protective effects of gemigliptin on renal fibrosis, particularly concerning its potential to upregulate the expression of fibroblast growth factor 21 (FGF21), remains incompletely understood. The purpose of this study was to investigate the gemigliptin’s renoprotective effects against TGF-β-induced renal fibrosis by enhancing the expression of fibroblast growth factor 21 in the cultured human proximal tubular epithelial cell line, HK-2.

Methods: HK-2 cells were maintained with keratinocyte-free medium according to the supplier’s recommendations, and exposed to the indicated doses of TGF-β, FGF21, and gemigliptin for 24 h. To elucidate the effect of FGF21, knockdown experiments were conducted by transfecting HK-2 cells with small interfering RNA targeting the fibroblast growth factor 21 for 24 h.

Results: Treatment of FGF21 effectively prevented TGF-β-induced renal fibrosis by attenuating TGF-β/Smad3 signaling pathway. Similarly, Gemigliptin showed protective effects against TGF-β-induced renal fibrosis by mitigating TGF-β/Smad3 signaling, which is achieved through the upregulation of FGF21 expression. However, the protective effects of gemigliptin were blocked when FGF21 expression was knockdowned in TGF-β-treated HK-2 Cells.

Conclusion: These results indicate that gemegliptin has the potential to confer protective effects against TGF-β-induced renal fibrosis by elavating FGF21 expression levels in the cultured human proximal tubular epithelial cells.