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)