Division of Endocrinology and Metabolism, Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Korea.
Department of Biomedical Science, Graduate School, Kyungpook National University, Daegu, Korea.
Diabetes Metab J. 2020 Feb;44(1):186-192. doi: 10.4093/dmj.2018.0271. Epub 2019 Oct 31.
Renal fibrosis is considered to be the final common outcome of chronic kidney disease. Dipeptidyl peptidase-4 (DPP-4) inhibitors have demonstrated protective effects against diabetic kidney disease. However, the anti-fibrotic effect of evogliptin, a DPP-4 inhibitor, has not been studied. Here, we report the beneficial effects of evogliptin on unilateral ureteral obstruction (UUO)-induced renal fibrosis in mice. Evogliptin attenuated UUO-induced renal atrophy and tubulointerstitial fibrosis. Immunohistochemistry and Western blotting demonstrated that evogliptin treatment inhibits pro-fibrotic gene expressions and extracellular matrix production. findings showed that the beneficial effects of evogliptin on renal fibrosis are mediated by inhibition of the transforming growth factor-β/Smad3 signaling pathway. The present study demonstrates that evogliptin is protective against UUO-induced renal fibrosis, suggesting that its clinical applications could extend to the treatment of kidney disease of non-diabetic origin.
肾纤维化被认为是慢性肾脏病的终末共同结局。二肽基肽酶-4（DPP-4）抑制剂已被证明对糖尿病肾病具有保护作用。然而，DPP-4 抑制剂依格列汀的抗纤维化作用尚未得到研究。在这里，我们报告了依格列汀对单侧输尿管梗阻（UUO）诱导的小鼠肾纤维化的有益作用。依格列汀减轻了 UUO 诱导的肾萎缩和肾小管间质纤维化。免疫组织化学和 Western blot 表明，依格列汀抑制促纤维化基因表达和细胞外基质产生。研究结果表明，依格列汀对肾纤维化的有益作用是通过抑制转化生长因子-β/Smad3 信号通路介导的。本研究表明，依格列汀对 UUO 诱导的肾纤维化具有保护作用，提示其临床应用可能扩展到治疗非糖尿病来源的肾脏疾病。
