Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Department of Integrated Therapy for Chronic Kidney Disease, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Department of Integrated Therapy for Chronic Kidney Disease, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Biochem Biophys Res Commun. 2020 May 7;525(3):767-772. doi: 10.1016/j.bbrc.2020.02.048. Epub 2020 Mar 6.
The accumulation of glucose degradation products (GDPs) can lead to tissue damage in patients with diabetes and those undergoing long-term peritoneal dialysis (PD). Angiogenesis is occasionally observed in the peritoneal membrane of patients undergoing PD, where it is associated with failure of ultrafiltration. To investigate the mechanism underlying the influence of angiogenesis on fluid absorption, we evaluated the effects of accumulation of the glucose degradation product methylglyoxal (MGO) on angiogenesis in vitro, and analyzed the association with angiogenesis in the peritoneal membrane. To this end, we measured the levels of vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF)-BB in cultured endothelial and smooth muscle cells after administration of MGO. The expression of PDGF-BB mRNA and protein decreased significantly after exposure to MGO, while the expression of VEGF mRNA increased (both P < 0.01). The expression of PDGF-Rβ mRNA in cultured smooth muscle cells did not change after administration of MGO, although the expression of VEGF mRNA increased (P < 0.01). We also evaluated the associations between the number of capillary vessels, peritoneal function, and the degree of MGO deposition using peritoneum samples collected from patients undergoing PD. The number of immature capillary vessels was significantly associated with peritoneal dysfunction and the degree of MGO accumulation (both P < 0.01). In conclusion, MGO enhances the production of VEGF and suppresses the production of PDGF-BB, potentially leading to disturbance of angiogenesis in the peritoneal membrane. Accumulation of MGO in the peritoneum may cause immature angiogenesis and peritoneal dysfunction.
葡萄糖降解产物（GDPs）的积累可导致糖尿病患者和长期接受腹膜透析（PD）治疗的患者发生组织损伤。在接受 PD 的患者的腹膜中偶尔会观察到血管生成，这与超滤失败有关。为了研究血管生成对液体吸收的影响机制，我们评估了葡萄糖降解产物甲基乙二醛（MGO）在体外对血管生成的影响，并分析了其与腹膜中血管生成的相关性。为此，我们测量了 MGO 给药后培养的内皮细胞和平滑肌细胞中血管内皮生长因子（VEGF）和血小板衍生生长因子（PDGF）-BB 的水平。暴露于 MGO 后，PDGF-BB mRNA 和蛋白的表达明显下降，而 VEGF mRNA 的表达增加（均 P < 0.01）。虽然 VEGF mRNA 的表达增加（P < 0.01），但培养的平滑肌细胞中 PDGF-Rβ mRNA 的表达在给予 MGO 后并未改变。我们还使用从接受 PD 的患者中收集的腹膜样本评估了毛细血管数量、腹膜功能和 MGO 沉积程度之间的相关性。未成熟毛细血管数量与腹膜功能障碍和 MGO 积累程度显著相关（均 P < 0.01）。总之，MGO 增强了 VEGF 的产生，抑制了 PDGF-BB 的产生，可能导致腹膜中血管生成紊乱。MGO 在腹膜中的积累可能导致不成熟的血管生成和腹膜功能障碍。
