Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Center for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
Commun Biol. 2021 Jan 29;4(1):144. doi: 10.1038/s42003-021-01652-x.
Peritoneal dialysis (PD) possesses multiple advantages for end stage renal disease. However, long-term PD triggers peritoneal fibrosis (PF). From the nationwide analysis of diabetic PD patients (n = 19,828), we identified the incidence of PD failure was significantly lower in diabetic patients treated with dipeptidyl peptidase 4 (DPP4) inhibitors. Experimental study further showed high concentration of glucose remarkably enhanced DPP4 to promote epithelial-mesenchymal transition (EMT) in the mesothelial cells. In chlorhexidine gluconate (CG)-induced PF model of rats, DPP4 expression was enriched at thickening peritoneum. Moreover, as to CG-induced PF model, DPP4 deficiency (F344/DuCrlCrlj strain), sitagliptin and exendin-4 treatments significantly inhibited DPP4 to reverse the EMT process, angiogenesis, oxidative stress, and inflammation, resulting in the protection from PF, preservation of peritoneum and the corresponding functional integrity. Furthermore, DPP4 activity was significantly correlated with peritoneal dysfunction. Taken together, DPP4 caused peritoneal dysfunction/PF, whereas inhibition of DPP4 protected the PD patients against PD failure.
腹膜透析（PD）在治疗终末期肾病方面具有多种优势。然而，长期 PD 会引发腹膜纤维化（PF）。通过对糖尿病 PD 患者（n=19828）的全国性分析，我们发现使用二肽基肽酶 4（DPP4）抑制剂治疗的糖尿病患者 PD 失败的发生率明显较低。实验研究进一步表明，高浓度葡萄糖可显著增强 DPP4 促进间皮细胞上皮间质转化（EMT）的作用。在葡萄糖酸洗必泰（CG）诱导的大鼠 PF 模型中，DPP4 表达在腹膜增厚处富集。此外，对于 CG 诱导的 PF 模型，DPP4 缺乏（F344/DuCrlCrlj 品系）、西他列汀和 exendin-4 治疗可显著抑制 DPP4 逆转 EMT 过程、血管生成、氧化应激和炎症，从而防止 PF、维持腹膜及其相应的功能完整性。此外，DPP4 活性与腹膜功能障碍显著相关。综上所述，DPP4 引起腹膜功能障碍/ PF，而抑制 DPP4 可保护 PD 患者免受 PD 失败的影响。
