Activation of hepatocyte growth factor in monkey stomach following gastric mucosal injury.
BACKGROUND
Hepatocyte growth factor (HGF) is involved in the proliferation and migration of various types of epithelial cells. HGF is produced as a single-chain precursor (pro-HGF) and functions after activation by HGF activator (HGFA). In this study, we aimed to examine the activation of pro-HGF to mature HGF and the expressions of HGF-related molecules, such as HGFA and HGFA inhibitor type 1 (HAI-1), in a monkey model of gastric mucosal injury.


METHODS
Gastric mucosal injury was induced in Japanese monkeys by administration of HCl using nasal-gastric tubes. HGF activation was evaluated by Western blotting and enzyme-linked immunosorbent assay (ELISA), and the expression of HGF, HGFA, HAI-1, and c-Met were examined by Northern blotting and immunohistochemistry.


RESULTS
Pro-HGF, but not mature HGF, was detected in normal gastric mucosa. When gastric mucosal injuries were induced, the expression of HGF significantly increased, and immunostaining of HGF was detected in fibroblasts in the gastric mucosa. In addition, conversion to mature HGF was observed in the injured gastric tissues, and mature HGF continued to increase for 48 h. HGFA was stably expressed in monkey livers, regardless of HCl administration. HAI-1 expression was detected in normal gastric mucosa, and its levels decreased after the induction of gastric mucosal injury.


CONCLUSIONS
These results indicate that pro-HGF is stored in normal gastric tissues, and suggest that its conversion to mature HGF, associated with HGFA and HAI-1, is important for the repair of gastric mucosal injury.
Hori
Takeshi
T
Second Department of Internal Medicine, Miyazaki Medical College, University of Miyazaki, 889-1601, Miyazaki, Kiyotake, Japan.
Ido
Akio
A
Uto
Hirofumi
H
Hasuike
Satoru
S
Moriuchi
Akihiro
A
Hayashi
Katsuhiro
K
Nakagawa
Shiro
S
Miyazawa
Keiji
K
Kitamura
Naomi
N
Tsubouchi
Hirohito
H
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D004797:Enzyme-Linked Immunosorbent Assay; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D015870:Gene Expression; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D006851:Hydrochloric Acid; D008251:Macaca; D008562:Membrane Glycoproteins / Q000378:metabolism; D012697:Serine Endopeptidases / Q000378:metabolism
D008562:Membrane Glycoproteins; D017228:Hepatocyte Growth Factor; C081092:HGF activator; D012697:Serine Endopeptidases; D006851:Hydrochloric Acid