Abstract:
Fibroblast growth factor 21 (FGF21), 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 other dipeptidyl peptidase-4 inhibitors are frequently used for the management of patients with type 2 diabetes. However, the protective effect of gemigliptin against renal fibrosis, particularly its potential to upregulate the expression of FGF21, remains incompletely understood. This study assessed the renoprotective effects of gemigliptin against TGF-β-induced renal fibrosis by enhancing the expression of FGF21 in the cultured human proximal tubular epithelial cell line HK-2. Treatment with FGF21 effectively prevented TGF-β-induced renal fibrosis by attenuating the TGF-β/Smad3 signaling pathway. Similarly, gemigliptin exhibited protective effects against TGF-β-induced renal fibrosis by mitigating TGF-β/Smad3 signaling through the upregulation of FGF21 expression. However, the protective effects of gemigliptin were blocked when FGF21 expression was knocked down in TGF-β-treated HK-2 cells. These results indicate that gemegliptin has the potential to exhibit protective effects against TGF-β-induced renal fibrosis by elevating FGF21 expression levels in cultured human proximal tubular epithelial cells.
摘要:
成纤维细胞生长因子21(FGF21),众所周知的代谢紊乱调节因子,显示出通过负调节转化生长因子β(TGF-β)/Smad3信号通路来预防肾纤维化的潜力。吉格列汀和其他二肽基肽酶-4抑制剂经常用于治疗2型糖尿病患者。然而,吉格列汀对肾脏纤维化的保护作用,特别是其上调FGF21表达的潜力仍未完全了解。这项研究通过增强培养的人近端肾小管上皮细胞系HK-2中FGF21的表达,评估了吉格列汀对TGF-β诱导的肾纤维化的肾脏保护作用。FGF21治疗通过减弱TGF-β/Smad3信号通路有效预防TGF-β诱导的肾纤维化。同样,吉格列汀通过上调FGF21表达来缓解TGF-β/Smad3信号传导,从而对TGF-β诱导的肾纤维化表现出保护作用。然而,当TGF-β处理的HK-2细胞中FGF21表达下调时,吉格列汀的保护作用被阻断。这些结果表明,吉格列汀有可能通过提高培养的人近端肾小管上皮细胞中的FGF21表达水平来表现出对TGF-β诱导的肾纤维化的保护作用。