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Published on: July 19, 2018
An integrin-activating peptide, PHSRN, ameliorates inhibitory effects of conventional peritoneal dialysis fluids on
Tetsu Miyamoto1, Masahito Tamura, Narutoshi Kabashima
1Second Department of Internal Medicine, University of Occupational and Environmental Health School of Medicine, Kitakyushu, Japan.
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.
Insights
The Pro-His-Ser-Arg-Asn (PHSRN) peptide promotes peritoneal membrane regeneration in dialysis patients. PHSRN counteracts harmful effects of dialysis fluids, improving wound healing and reducing fibrosis.
Area of Science:
- Regenerative Medicine
- Cell Biology
- Nephrology
Background:
- Peritoneal dialysis fluids (PDFs) can cause pathological changes, including membrane dysfunction and fibrosis.
- Fibronectin cell-binding domains, like Pro-His-Ser-Arg-Asn (PHSRN) peptide, are known to activate integrins and aid wound healing.
Purpose of the Study:
- To investigate the therapeutic potential of PHSRN peptide in mitigating peritoneal membrane damage caused by PDFs.
- To assess the impact of PHSRN on peritoneal remodelling in a rat model of peritoneal dialysis.
Main Methods:
- A rat model with a stripped peritoneal mesothelial monolayer received PDFs with or without PHSRN or a control peptide (HSPNR).
- Effects on cell motility and signaling were analyzed in cultured rat peritoneal mesothelial cells (RPMCs) and fibroblasts (NRKs).
Main Results:
- PHSRN significantly improved mesothelial regeneration compared to PDFs alone, restoring it to control levels.
- PDFs increased submesothelial tissue thickening and inflammatory cell infiltration, effects ameliorated by PHSRN.
- PHSRN reversed PDF-induced inhibition of cell motility and focal adhesion kinase signaling in RPMCs and NRKs.
Conclusions:
- PHSRN peptide demonstrates beneficial effects on peritoneal regeneration and wound healing.
- PHSRN counteracts the detrimental effects of conventional PDFs on integrin-mediated healing processes.
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