The loss of local HGF, an endogenous gastrotrophic factor, leads to mucosal injuries in the stomach of mice.
The stomach is constantly exposed to mechanical and chemical stresses. Under persistent damages, epithelial cell proliferation is required to maintain mucosal integrity. Nevertheless, which ligand system(s) is physiologically involved in gastric defense remains unclear. Herein, we provide evidence that HGF is a key "natural ligand" to reverse gastric injury. The injection of cisplatin in mice led to the loss of HGF in the gastric interstitium, associated with the decrease in proliferating epithelium and the progression of mucotitis. When c-Met tyrosine phosphorylation was abolished by anti-HGF IgG, mucosal cell proliferation became faint, leading to delayed recovery from mucotitis, and vice versa in cases of HGF supplementation. Our findings indicate that: (1) HGF/c-Met signal on mucosa is needed to restore gastric injuries; and (2) the loss of local HGF leads to manifestation of gastric lesions. This study provides a rationale that explains why HGF supplement is useful for reversing gastric diseases.
Division of Molecular Regenerative Medicine, Department of Molecular Regenerative Medicine, Osaka University Graduate School of Medicine, Yamadaoka 2-2-B7, Suita 565-0871, Japan.
Rie
R
Nakahira
Shinya
S
Mizuno
Toshiki
T
Yoshimine
Toshikazu
T
Nakamura
D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D002945:Cisplatin / Q000633:toxicity; D005260:Female; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects / Q000473:pathology*; D017228:Hepatocyte Growth Factor / Q000276:immunology / Q000494:pharmacology / Q000502:physiology*; D007074:Immunoglobulin G / Q000494:pharmacology; D051379:Mice; D008813:Mice, Inbred ICR; D010766:Phosphorylation; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D013272:Stomach Diseases / Q000378:metabolism / Q000473:pathology*; D013276:Stomach Ulcer / Q000378:metabolism / Q000473:pathology
D007074:Immunoglobulin G; D011994:Recombinant Proteins; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met; D002945:Cisplatin