Insulin-like growth factor I plays a role in gastric wound healing: evidence using a zinc derivative, polaprezinc, and an in vitro rabbit wound repair model.

Background: Although the detailed mechanism is unclear, zinc and its deriva tive, polaprezinc, have been reported to accelerate gastric ulcer healing i n vivo. Aim: To investigate the detailed cellular mechanism of polaprezinc on gastr ic epithelial cells and fibroblasts with special attention to insulin-like growth factor I (IGF-I). Methods: Isolated rabbit gastric epithelial cells formed a complete monolay er, from which a circular artificial wound with constant size was made, The restoration process was monitored by measuring wound size up to 48 h, Eith er polaprezinc, IGF-I, fibroblast conditioned medium or neutralized medium conditioned by anti-IGF-I antibody was added at the time of wounding. The e xpression of mRNA of IGF-I, hepatocyte growth factor (HGF) and transforming growth factor cc (TGF-a) in fibroblasts with or without polaprezinc treatm ent was tested using reverse transcription polymerase chain reaction (RT-PC R), Gastric epithelial cell proliferation was also examined by bromodeoxyur idine (BrdU) staining. Results: IGF-I and fibroblast conditioned medium treatment accelerated gast ric epithelial restoration which included cell migration and proliferation. However, polaprezine and neutralized conditioned medium treatment did not accelerate epithelial repair. RT-PCR for growth factor mRNA revealed the IG F-I mRNA expression in fibroblasts was increased after treatment with polap rezinc. Conclusion: Polaprezinc induced IGF-I production from mesenchymal cells, re sulting in stimulation of epithelial cell restoration through a paracrine p athway. IGF-I may play an important role in gastric wound repair.