Shioshita K, Miyazaki M, Ozono Y, Abe K, Taura K, Harada T, Koji T, Taguchi T, Kohno S
The Second Department of Internal Medicine, Nagasaki University School of Medicine, Sakamoto, Japan.
Kidney Int. 2000 Feb;57(2):619-31. doi: 10.1046/j.1523-1755.2000.00883.x.
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.
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 end-stage renal disease prior to induction of CAPD.
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.
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.
腹膜硬化以胶原蛋白积聚为特征，是持续性非卧床腹膜透析（CAPD）治疗中的一种严重并发症。热休克蛋白47（HSP47）是一种胶原蛋白特异性分子伴侣，与胶原蛋白合成密切相关。
我们通过免疫组织化学法测定了CAPD患者腹膜组织中HSP47和HSP70（非胶原蛋白合成特异性）的表达。同时对胶原蛋白III、α-平滑肌肌动蛋白（α-SMA）和CD68（巨噬细胞标志物）的组织进行染色。32份腹膜样本分为三组（A1组，11例无超滤丢失患者；A2组，9例有超滤丢失患者；B组，12份CAPD诱导前患有终末期肾病的标本）。
B组腹膜组织中HSP47、HSP70和胶原蛋白III的染色较淡，仅有少数细胞α-SMA和CD68呈阳性。相比之下，CAPD患者纤维化腹膜标本中增厚的结缔组织区域表达HSP47、HSP70和胶原蛋白III。A2组中HSP47、HSP70、胶原蛋白III和α-SMA的表达水平以及CD68阳性细胞数量显著高于A1组和B组。HSP47/HSP70阳性细胞为间皮细胞、脂肪细胞和α-SMA阳性肌成纤维细胞。此外，难治性腹膜炎患者腹膜标本中HSP47的表达水平显著高于无难治性腹膜炎患者，且CAPD治疗超过60个月的患者HSP47表达水平显著高于CAPD治疗少于60个月的患者。
我们的结果表明，CAPD治疗可能诱导腹膜组织中的热休克蛋白，且CAPD患者的腹膜炎可能至少通过HSP47表达和慢性巨噬细胞浸润与腹膜硬化的进展相关。我们的数据还表明，此类患者腹膜硬化的进展与腹膜超滤功能的恶化有关。
