Roles of hepatocyte growth factor and its receptor Met during gastric ulcer healing in rats.
OBJECTIVE
It is unclear which growth factors are primarily responsible for stimulating gastric ulcer healing. The roles of hepatocyte growth factor (HGF) and Met/HGF receptor during gastric ulcer healing were studied in rats.


METHODS
HGF and Met/HGF receptor were located and quantified by in situ hybridization and immunohistochemistry during experimental gastric ulcer healing. The in vivo effects of exogenous recombinant human HGF on cell proliferation and ulcer healing were assessed and compared with those of placebo and omeprazole treatment.


RESULTS
Compared with intact oxyntic mucosa, messenger RNA (mRNA) of HGF and met was substantially greater in the ulcerated region on days 3 and 15. HGF mRNA was located in stromal cells between the regenerative glands and in the arterial vessels of submucosal tissue, whereas met mRNA was located in the epithelial cells of the regenerative glands. After cryoinjury, immunoreactivity for the Met/HGF receptor was absent on day 3, reappeared on day 8, and was overexpressed on day 15. Exogenous recombinant human HGF had no effect on the ulcer healing parameters over days 3-8, but it did increase epithelial cell proliferation in the ulcer margin over days 8-15.


CONCLUSIONS
These data suggest that HGF mediates specific tissue interactions between mesenchyme and epithelia during gastric ulcer healing.
Schmassmann
A
A
Gastrointestinal Unit, Inselspital, University Hospital, Bern, Switzerland.
Stettler
C
C
Poulsom
R
R
Tarasova
N
N
Hirschi
C
C
Flogerzi
B
B
Matsumoto
K
K
Nakamura
T
T
Halter
F
F
D000199:Actins / Q000235:genetics; D000818:Animals; D016466:CHO Cells; D002455:Cell Division / Q000502:physiology; D006224:Cricetinae; D004724:Endoscopy; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000473:pathology; D006133:Growth Substances / Q000235:genetics; D017228:Hepatocyte Growth Factor / Q000493:pharmacokinetics / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D008297:Male; D009077:Mucins; D009124:Muscle Proteins; D009479:Neuropeptides; D010455:Peptides / Q000235:genetics; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins; D013276:Stomach Ulcer / Q000503:physiopathology*; D013690:Television; D000071164:Trefoil Factor-2; D000071165:Trefoil Factor-3; D014945:Wound Healing / Q000502:physiology*
D000199:Actins; D006133:Growth Substances; D009077:Mucins; D009124:Muscle Proteins; D009479:Neuropeptides; D010455:Peptides; D012333:RNA, Messenger; D011994:Recombinant Proteins; C099037:TFF3 protein, rat; D000071164:Trefoil Factor-2; D000071165:Trefoil Factor-3; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met