論文 - 詳細
RRC ID | 38230 |
---|---|
著者 | Miyamoto T, Tamura M, Kabashima N, Serino R, Shibata T, Furuno Y, Miyazaki M, Baba R, Sato N, Doi Y, Okazaki M, Otsuji Y. |
タイトル | An integrin-activating peptide, PHSRN, ameliorates inhibitory effects of conventional peritoneal dialysis fluids on peritoneal wound healing. |
ジャーナル | Nephrol Dial Transplant |
Abstract |
BACKGROUND: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. METHODS: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). RESULTS: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. CONCLUSIONS:These results suggest that PHSRN has beneficial effects on peritoneal regeneration by reducing the inhibitory effects of conventional PDF on integrin-mediated wound healing. |
巻・号 | 25(4) |
ページ | 1109-19 |
公開日 | 2010-4-1 |
DOI | 10.1093/ndt/gfp601 |
PII | gfp601 |
PMID | 19926720 |
MeSH | Animals Blotting, Western Cell Movement Cell Proliferation Cells, Cultured Dialysis Solutions Epithelial Cells / metabolism Epithelial Cells / pathology Female Fibronectins / pharmacology* Immunoenzyme Techniques Immunoprecipitation Integrins / metabolism* Peptide Fragments / pharmacology* Peritoneal Dialysis* Peritoneum / drug effects* Peritoneum / injuries* Peritoneum / pathology Rats Rats, Wistar Wound Healing / drug effects* |
IF | 4.531 |
引用数 | 6 |
WOS 分野 | UROLOGY & NEPHROLOGY TRANSPLANTATION |
リソース情報 | |
ヒト・動物細胞 | NRK(RCB0043) |