title: An integrin-activating peptide, PHSRN, ameliorates inhibitory effects of conventional peritoneal dialysis fluids on peritoneal wound healing.
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.
authors.affiliation: Second Department of Internal Medicine, University of Occupational and Environmental Health School of Medicine, Kitakyushu, Japan.
authors.forename: Tetsu
authors.initials: T
authors.lastname: Miyamoto
authors.forename: Masahito
authors.initials: M
authors.lastname: Tamura
authors.forename: Narutoshi
authors.initials: N
authors.lastname: Kabashima
authors.forename: Ryota
authors.initials: R
authors.lastname: Serino
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Shibata
authors.forename: Yumi
authors.initials: Y
authors.lastname: Furuno
authors.forename: Mieko
authors.initials: M
authors.lastname: Miyazaki
authors.forename: Ryoko
authors.initials: R
authors.lastname: Baba
authors.forename: Nagahiro
authors.initials: N
authors.lastname: Sato
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Doi
authors.forename: Masahiro
authors.initials: M
authors.lastname: Okazaki
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Otsuji
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D015314:Dialysis Solutions; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D005353:Fibronectins / Q000494:pharmacology*; D007124:Immunoenzyme Techniques; D047468:Immunoprecipitation; D016023:Integrins / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology*; D010530:Peritoneal Dialysis; D010537:Peritoneum / Q000187:drug effects* / Q000293:injuries* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D015314:Dialysis Solutions; D005353:Fibronectins; D016023:Integrins; D010446:Peptide Fragments; C495978:prolyl-histidyl-seryl-arginyl-asparagine