Second Department of Internal Medicine, University of Occupational and Environmental Health School of Medicine, Kitakyushu, Japan.
Nephrol Dial Transplant. 2010 Apr;25(4):1109-19. doi: 10.1093/ndt/gfp601. Epub 2009 Nov 19.
Bioincompatible peritoneal dialysis fluids (PDFs) cause pathological changes in the peritoneal membrane, related to membrane dysfunction and progressive peritoneal fibrosis. We investigated the effects of Pro-His-Ser-Arg-Asn (PHSRN) peptide, one of the fibronectin cell-binding domains that activates integrins and reinforces wound healing, on peritoneal remodelling in a rat peritoneal injury model undergoing peritoneal dialysis.
The peritoneal mesothelial monolayer was removed by a stripping procedure in rats receiving conventional high glucose-containing PDF supplemented with or without PHSRN or control His-Ser-Pro-Asn-Hrg (HSPNR) peptides. Effects of PHSRN on cell motility and signalling molecules were examined in cultured rat peritoneal mesothelial cells (RPMCs) and normal rat kidney fibroblasts (NRKs).
The cytokeratin- and HBME-1-positive mesothelial cell monolayer was selectively removed by the procedure. By day 6, HBME-1-positive cells had regenerated to 53.3 +/- 6.5% of the peritoneal surface in the control group. Regeneration of the mesothelial layer was delayed in the PDF group (35.2 +/- 10.2%, P < 0.05), but PHSRN reversed the effects of PDF (51.7 +/- 9.6%, P < 0.05). PDF treatment increased thickening of granulomatous submesothelial tissue and numbers of ED1-, CD31- and alpha-smooth muscle actin-positive cells, but PHSRN ameliorated these effects. HSPNR had no effects on mesothelial regeneration or peritoneal wound healing. PHSRN, but not HSPNR, recovered glucose-induced inhibition of cell motility and phosphorylation of focal adhesion kinase and its downstream p130(Cas) in RPMCs and NRKs.
These results suggest that PHSRN has beneficial effects on peritoneal regeneration by reducing the inhibitory effects of conventional PDF on integrin-mediated wound healing.
生物不相容性腹膜透析液（PDF）可导致腹膜发生病理性改变，与膜功能障碍和进行性腹膜纤维化有关。我们研究了 Pro-His-Ser-Arg-Asn（PHSRN）肽对接受常规含高葡萄糖 PDF 腹膜透析的大鼠腹膜损伤模型中腹膜重塑的影响。该肽是纤连蛋白细胞结合域之一，可激活整合素并加强伤口愈合。
通过剥离程序去除大鼠腹膜间皮单层，接受常规高葡萄糖 PDF 补充或不补充 PHSRN 或对照 His-Ser-Pro-Asn-Hrg（HSPNR）肽的大鼠。在培养的大鼠腹膜间皮细胞（RPMCs）和正常大鼠肾成纤维细胞（NRKs）中，研究了 PHSRN 对细胞迁移和信号分子的影响。
该程序可选择性去除细胞角蛋白和 HBME-1 阳性间皮细胞单层。在对照组中，第 6 天时 HBME-1 阳性细胞再生至腹膜表面的 53.3±6.5%。在 PDF 组中，间皮层的再生延迟（35.2±10.2%，P<0.05），但 PHSRN 逆转了 PDF 的作用（51.7±9.6%，P<0.05）。PDF 处理增加了肉芽状亚腹膜组织的增厚和 ED1、CD31 和 α-平滑肌肌动蛋白阳性细胞的数量，但 PHSRN 改善了这些作用。HSPNR 对间皮再生或腹膜伤口愈合没有影响。PHSRN 而非 HSPNR 恢复了葡萄糖诱导的 RPMCs 和 NRKs 中细胞迁移和粘着斑激酶及其下游 p130（Cas）磷酸化的抑制作用。
这些结果表明，PHSRN 通过减少常规 PDF 对整合素介导的伤口愈合的抑制作用，对腹膜再生具有有益的影响。
