Expression of heat shock proteins 47 and 70 in the peritoneum of patients on continuous ambulatory peritoneal dialysis
Expression of heat shock proteins 47 and 70 in the peritoneum of patients on continuous ambulatory peritoneal dialysis
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DOI：
10.1046/j.1523-1755.2000.t01-1-00883.x
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发表时间：
2000-02-01
影响因子：
19.6
通讯作者：
Kohno, S
中科院分区：
文献类型：
--
作者：
Shioshita, K;Miyazaki, M;Kohno, S
背景资料。腹膜硬化症是持续非卧床腹膜透析(CAPD)治疗中的严重并发症，以胶原堆积为特征。热休克蛋白47(HSP47)是一种胶原特异的分子伴侣，与胶原的合成密切相关。采用免疫组织化学方法检测CAPD患者腹膜组织中HSP47和HSP70的表达。III型胶原、α-平滑肌肌动蛋白(α-SMA)和CD68(巨噬细胞的标志物)的组织也被染色。将32例腹膜标本分为3组，A1组11例无超滤丢失，A2组9例超滤丢失，B组12例CAPD诱导前有终末期肾病。B组腹膜组织中HSP47、HSP70和III型胶原表达较弱，仅少数细胞表达α-SMA和CD68。相反，在CAPD患者纤维化腹膜组织中，HSP47、HSP70和III型胶原在增厚的结缔组织中表达。A2组HSP47、HSP70、III型胶原和α-SMA的表达水平及CD68阳性细胞数均显著高于A1和B组。HSP47/HSP70阳性细胞包括间皮细胞、脂肪细胞和α-SMA阳性的肌成纤维细胞。此外，难治性腹膜炎患者腹膜组织中HSP47的表达水平显著高于无腹膜炎患者，且CAPD治疗时间>60个月的患者HSP47的表达水平显著高于CAPD时间<60个月的患者。我们的结果表明，CAPD治疗可诱导腹膜组织中的HSPs，CAPD患者的腹膜炎可能至少通过HSP47的表达和慢性巨噬细胞的浸润与腹膜硬化的进展有关。我们的数据还表明腹膜硬化症的进展与腹膜超滤功能的恶化有关。
Background. Peritoneal sclerosis, characterized by collagen accumulation, is a serious complication in continuous ambulatory peritoneal dialysis (CAPD) therapy. Heat shock protein 47 (HSP47) is a collagen-specific molecular chaperon and is closely associated with collagen synthesis.Methods. We determined the expression of HSP47 and HSP70 (nonspecific for collagen synthesis) by immunohistochemistry in peritoneal tissues of patients on CAPD. The tissue for collagen III, alpha-smooth muscle actin (alpha-SMA), and CD68 (a marker for macrophages) were also stained. Thirty-two peritoneal samples were divided into three groups (group A1, 11 patients who had no ultrafiltration loss; group A2, 9 patients who had ultrafiltration loss; and group B, 12 specimens who had endstage renal disease prior to induction of CAPD.Results. In group B, staining for HSP47, HSP70, and collagen III in peritoneal tissues was faint, and only a few cells were positive for alpha-SMA and CD68. In contrast, HSP47, HSP70, and collagen III were expressed in areas of thickened connective tissues in fibrotic peritoneal specimens of CAPD patients. The expression level of HSP47, HSP70, collagen III, and alpha-SMA and the number of CD68-positive cells in group A2 were significantly higher than those in groups A1 and B. HSP47/HSP70-positive cells were mesothelial cells, adipocytes, and alpha-SMA-positive myofibroblasts. Furthermore, the expression level of HSP47 was significantly higher in peritoneal specimens from patients with refractory peritonitis than without it and was significantly higher in patients with more than 60 months of CAPD therapy than that in patients with less than 60 months of CAPD.Conclusion. Our results indicate that CAPD therapy may induce HSPs in the peritoneal tissue, and that peritonitis in CAPD patients may be associated with the progression of peritoneal sclerosis at least through HSP47 expression and chronic macrophage infiltration. Our data also suggest that the progression of peritoneal sclerosis in such patients is associated with deterioration of peritoneal ultrafiltration function.