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

Aliment Pharmacol Ther. 1998 Nov;12(11):1131-8. doi: 10.1046/j.1365-2036.1998.00408.x.

Abstract

Background: Although the detailed mechanism is unclear, zinc and its derivative, polaprezinc, have been reported to accelerate gastric ulcer healing in vivo.

Aim: To investigate the detailed cellular mechanism of polaprezinc on gastric epithelial cells and fibroblasts with special attention to insulin-like growth factor I (IGF-I).

Methods: Isolated rabbit gastric epithelial cells formed a complete monolayer, from which a circular artificial wound with constant size was made. The restoration process was monitored by measuring wound size up to 48 h. Either polaprezinc, IGF-I, fibroblast conditioned medium or neutralized medium conditioned by anti-IGF-I antibody was added at the time of wounding. The expression of mRNA of IGF-I, hepatocyte growth factor (HGF) and transforming growth factor alpha (TGF-alpha) in fibroblasts with or without polaprezinc treatment was tested using reverse transcription polymerase chain reaction (RT-PCR). Gastric epithelial cell proliferation was also examined by bromodeoxyuridine (BrdU) staining.

Results: IGF-I and fibroblast conditioned medium treatment accelerated gastric epithelial restoration which included cell migration and proliferation. However, polaprezinc and neutralized conditioned medium treatment did not accelerate epithelial repair. RT-PCR for growth factor mRNA revealed the IGF-I mRNA expression in fibroblasts was increased after treatment with polaprezinc.

Conclusion: Polaprezinc induced IGF-I production from mesenchymal cells, resulting in stimulation of epithelial cell restoration through a paracrine pathway. IGF-I may play an important role in gastric wound repair.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Southern
  • Carnosine / analogs & derivatives*
  • Carnosine / pharmacology
  • Cell Division / drug effects
  • Cell Movement / drug effects
  • Cells, Cultured
  • Fibroblasts / metabolism
  • Gastric Mucosa / cytology
  • Gastric Mucosa / drug effects*
  • Gene Expression
  • Growth Substances / analysis
  • Insulin-Like Growth Factor I / genetics
  • Insulin-Like Growth Factor I / pharmacology*
  • Male
  • Mesoderm
  • Organometallic Compounds / pharmacology*
  • RNA, Messenger / metabolism
  • Rabbits
  • Reverse Transcriptase Polymerase Chain Reaction
  • Wound Healing / drug effects*
  • Zinc Compounds

Substances

  • Growth Substances
  • Organometallic Compounds
  • RNA, Messenger
  • Zinc Compounds
  • polaprezinc
  • Insulin-Like Growth Factor I
  • Carnosine