Impacts of icodextrin on integrin-mediated wound healing of peritoneal mesothelial cells

• Published in: Life sciences (1973) 2012-06, Vol.90 (23-24), p.917-923
• Main Authors: Matsumoto, Mika, Tamura, Masahito, Miyamoto, Tetsu, Furuno, Yumi, Kabashima, Narutoshi, Serino, Ryota, Shibata, Tatsuya, Kanegae, Kaori, Takeuchi, Masaaki, Abe, Haruhiko, Okazaki, Masahiro, Otsuji, Yutaka
• Format: Article
• Language: English
• Subjects: adhesion; adverse effects; Animals; biocompatibility; Biocompatibility of peritoneal dialysate; Blotting, Western; Cell adhesion; Cell Adhesion - drug effects; Cell migration; cell movement; Cell Movement - drug effects; Continuous ambulatory peritoneal dialysis; dialysis; Dialysis Solutions - pharmacology; Dialysis Solutions - toxicity; fibronectins; Focal adhesion kinase; Focal Adhesion Protein-Tyrosine Kinases - metabolism; Glucans - pharmacology; Glucans - toxicity; glucose; Glucose - pharmacology; Glucose - toxicity; Icodextrin; immunocytochemistry; Integrins - metabolism; Male; metabolites; Peritoneal Dialysis - methods; Peritoneum - cytology; Peritoneum - drug effects; Peritoneum - pathology; phosphorylation; Phosphorylation - drug effects; Rats; Rats, Wistar; tissue repair; tyrosine; Tyrosine - metabolism; Western blotting; Wound Healing - drug effects
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2012.04.036

Exposure to glucose and its metabolites in peritoneal dialysis fluid (PDF) results in structural alterations of the peritoneal membrane. Icodextrin-containing PDF eliminates glucose and reduces deterioration of peritoneal membrane function, but direct effects of icodextrin molecules on peritoneal mesothelial cells have yet to be elucidated. We compared the impacts of icodextrin itself with those of glucose under PDF-free conditions on wound healing processes of injured mesothelial cell monolayers, focusing on integrin-mediated cell adhesion mechanisms. Regeneration processes of the peritoneal mesothelial cell monolayer were investigated employing an in vitro wound healing assay of cultured rat peritoneal mesothelial cells treated with icodextrin powder- or glucose-dissolved culture medium without PDF, as well as icodextrin- or glucose-containing PDF. The effects of icodextrin on integrin-mediated cell adhesions were examined by immunocytochemistry and Western blotting against focal adhesion kinase (FAK). Cell migration over fibronectin was inhibited in conventional glucose-containing PDF, while icodextrin-containing PDF exerted no significant inhibitory effects. Culture medium containing 1.5% glucose without PDF also inhibited wound healing of mesothelial cells, while 7.5% icodextrin-dissolved culture medium without PDF had no inhibitory effects. Glucose suppressed cell motility by inhibiting tyrosine phosphorylation of FAK, formation of focal adhesions, and cell spreading, while icodextrin had no effects on any of these mesothelial cell functions. Our results demonstrate icodextrin to have no adverse effects on wound healing processes of peritoneal mesothelial cells. Preservation of integrin-mediated cell adhesion might be one of the molecular mechanisms accounting for the superior biocompatibility of icodextrin-containing PDF.