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 derivative, polaprezinc, have been reported to accelerate gastric ulcer healing in vivo.


OBJECTIVE
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.


CONCLUSIONS
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.
Watanabe
S
S
Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan.
Wang
X E
XE
Hirose
M
M
Kivilioto
T
T
Osada
T
T
Miwa
H
H
Oide
H
H
Kitamura
T
T
Yoneta
T
T
Seto
K
K
Sato
N
N
D000818:Animals; D015139:Blotting, Southern; D002336:Carnosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D005347:Fibroblasts / Q000378:metabolism; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects*; D015870:Gene Expression; D006133:Growth Substances / Q000032:analysis; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000494:pharmacology*; D008297:Male; D008648:Mesoderm; D009942:Organometallic Compounds / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014945:Wound Healing / Q000187:drug effects*; D017967:Zinc Compounds
D006133:Growth Substances; D009942:Organometallic Compounds; D012333:RNA, Messenger; D017967:Zinc Compounds; C061957:polaprezinc; D007334:Insulin-Like Growth Factor I; D002336:Carnosine