Naiki Y, Matsuo K, Matsuoka T, Maeda Y
Department of Internal Medicine, Division of Hematology, Nephrology and Rheumatology, Kinki University School of Medicine, 377-2, Ohno-Hogashi, Osaka-Sayama, Osaka 589 8511, Japan.
Int J Artif Organs. 2005 Feb;28(2):141-9. doi: 10.1177/039139880502800210.
Human peritoneal mesothelial cells (HPMCs) play an important role in peritoneal functions. During long term peritoneal dialysis, it has been reported that HPMCs are damaged by high glucose solution via the signal of transforming growth factor (TGF)-beta1 produced by HPMCs. In this study, we focused on the effect of hepatocyte growth factor (HGF), known as an anti-fibrotic and anti-TGF-beta1 agent, on HPMCs damaged by high glucose solution. HPMCs were isolated from specimens of the omentum from nonuremic patients after informed consent had been obtained. After confirming adhesion for 6 hours, 100 microL of DMEM with 0.5%FCS were added at different concentrations (D-glucose; 6, 30 mM) with or without HGF (10, 30, 100 ng/mL) for 48 hours. We examined the effects of a high concentration of glucose and then focused on following four critical points: 1) the production of HGF from HPMCs exposed to a high concentration of glucose, 2) the expression of c-Met on HPMCs, 3) the viability of those cells, and 4) matrix metalloproteinase-2 (MMP-2) and tissue inhibitors of metalloproteinase-2 (TIMP-2). The following significant changes are described herein: high glucose solution and TGF-beta1 i) decreased HGF production from HPMCs and ii) up-regulated expression of c-Met on HPMCs, and addition of HGF iii) restored viability of HPMCs damaged by glucose, iv) suppressed TGF-beta1 production by HGF, and v) induced up-regulation of MMP-2 and decreased TIMP-2 production by HPMCs. Levels of HGF decreased by high concentrations of glucose in the peritoneal cavity may induce the loss of HPMCs and thereby result in peritoneal fibrosis. These results suggest that HGF is an effective agent in the regeneration of peritoneal membrane damaged by high glucose solution.
人腹膜间皮细胞（HPMCs）在腹膜功能中发挥着重要作用。据报道，在长期腹膜透析过程中，HPMCs会被高糖溶液通过其自身产生的转化生长因子（TGF）-β1信号所损伤。在本研究中，我们聚焦于肝细胞生长因子（HGF），一种已知的抗纤维化和抗TGF-β1因子，对被高糖溶液损伤的HPMCs的影响。在获得知情同意后，从非尿毒症患者的大网膜标本中分离出HPMCs。在确认细胞贴壁6小时后，加入不同浓度（D-葡萄糖；6、30 mM）含或不含HGF（10、30、100 ng/mL）的100 μL含0.5%胎牛血清的DMEM，培养48小时。我们检测了高浓度葡萄糖的影响，然后聚焦于以下四个关键点：1）暴露于高浓度葡萄糖的HPMCs中HGF的产生；2）HPMCs上c-Met的表达；3）这些细胞的活力；4）基质金属蛋白酶-2（MMP-2）和金属蛋白酶组织抑制剂-2（TIMP-2）。本文描述了以下显著变化：高糖溶液和TGF-β1 i）降低了HPMCs中HGF的产生，ii）上调了HPMCs上c-Met的表达，而添加HGF iii）恢复了被葡萄糖损伤的HPMCs的活力，iv）抑制了HGF产生的TGF-β1，v）诱导HPMCs上调MMP-2表达并降低TIMP-2产生。腹腔内高浓度葡萄糖导致的HGF水平降低可能会导致HPMCs丢失，进而导致腹膜纤维化。这些结果表明，HGF是一种有效促进被高糖溶液损伤的腹膜再生的药物。
