Long-term peritoneal dialysate exposure modulates expression of membrane complement regulators in human peritoneal mesothelial cells.

Long-term peritoneal dialysate exposure modulates expression of membrane complement regulators in human peritoneal mesothelial cells.
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DOI:
10.3389/fmed.2022.972592
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发表时间:
2022
影响因子:
3.9
通讯作者:
--
中科院分区:
医学3区
文献类型:
--
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膜补体调节因子(CReg)CD 46、CD 55和CD 59在人腹膜间皮细胞上高度表达。然而,间皮细胞CReg如何根据患者的腹膜透析(PD)史而变化仍不清楚。因此,我们检查了来自PD患者的原代培养的间皮细胞(人腹膜间皮细胞; HPMCs)中CReg的纵向变化,并检查了PD液(PDF)的哪些组分在体外影响CReg。我们测量了PD患者过夜居住的PDF中可溶性C5 b-9的水平,并使用流式细胞术和聚合酶链反应评估了PD治疗间隔1年时从PDF收集的HPMCs上CRegs表达的变化。我们还使用Met 5A人间皮细胞系评估了CReg表达随PDF的每种组分(葡萄糖、乳酸和pH)刺激的变化。1年内PDF中sC 5 b-9水平显著下降,而HPMCs中CD 46和CD 59蛋白和mRNA表达显著增加。分析Met-5A细胞,我们观察到三种CReg的表达以浓度依赖性的方式被葡萄糖和乳酸增加,但相反地,CReg的表达被较低的pH刺激降低。PD的历史可能会影响HPMCs通过PDF的性质,如葡萄糖,乳酸和pH值的CRegs的表达。这些结果表明,间皮细胞可能会改变CRegs的表达,以保护腹膜和PDF的存在可能会影响与补体系统相关的腹膜稳态。
The membrane complement regulators (CRegs) CD46, CD55, and CD59 are highly expressed on human peritoneal mesothelial cells. However, how mesothelial CRegs change according to the peritoneal dialysis (PD) history of patients has remained unclear. We therefore examined longitudinal changes in CRegs in primary cultured mesothelial cells from PD patients (human peritoneal mesothelial cells; HPMCs) and examined which components of PD fluid (PDF) affect CRegs in vitro. We measured levels of soluble C5b-9 in overnight-dwelling PDF in PD patients and also evaluated changes in CRegs expression on HPMCs collected from PDF using flow cytometry and polymerase chain reaction at a 1-year interval of PD therapy. We also evaluated changes in CReg expressions with stimulation by each component of PDF (glucose, lactic acid and pH) using the Met5A human mesothelial cell line. Levels of sC5b-9 in PDF decreased significantly during 1 year, while expressions of CD46 and CD59 proteins and mRNAs increased significantly in HPMCs during 1 year. Analyzing Met-5A cells, we observed that expressions of the three CRegs were increased by glucose and lactic acid in a concentration-dependent manner, but conversely that expressions of CRegs were decreased by lower pH stimulation. History of PD might influence expression of CRegs by HPMCs through properties of PDF such as glucose, lactic acid, and pH. These results suggest that mesothelial cells may alter expression of CRegs for the purpose of protecting the peritoneum and the presence of PDF might affect peritoneal homeostasis associated with the complement system.
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