An integrin-activating peptide, PHSRN, ameliorates inhibitory effects of conventional peritoneal dialysis fluids on peritoneal wound healing.
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.
Miyamoto
Tetsu
T
Second Department of Internal Medicine, University of Occupational and Environmental Health School of Medicine, Kitakyushu, Japan.
Tamura
Masahito
M
Kabashima
Narutoshi
N
Serino
Ryota
R
Shibata
Tatsuya
T
Furuno
Yumi
Y
Miyazaki
Mieko
M
Baba
Ryoko
R
Sato
Nagahiro
N
Doi
Yoshiaki
Y
Okazaki
Masahiro
M
Otsuji
Yutaka
Y
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*
D015314:Dialysis Solutions; D005353:Fibronectins; D016023:Integrins; D010446:Peptide Fragments; C495978:prolyl-histidyl-seryl-arginyl-asparagine