Loss of HGF activator inhibits foveolar hyperplasia induced by oxyntic atrophy without altering gastrin levels.
Spasmolytic polypeptide/trefoil family factor 2 expressing metaplasia (SPEM) is induced by oxyntic atrophy and is known as a precancerous or paracancerous lesion. We now have sought to determine whether hepatocyte growth factor (HGF) influences the development of SPEM and oxyntic atrophy. DMP-777, a parietal cell ablating reagent, was administered to HGF activator (HGFA)-deficient mice and wild-type mice. Gastric mucosal lineage changes were analyzed in the DMP-777 treatment phase and recovery phase. Both wild-type and HGFA knockout mice showed SPEM, and there was no difference in SPEM development. However, after cessation of DMP-777, HGFA-deficient mice showed delayed recovery from SPEM compared with wild-type mice. Foveolar cell hyperplasia and the increase in proliferating cells after parietal cell loss were reduced in HGFA-deficient mice. The HGFA does not affect emergence of SPEM. However, the absence of HGFA signaling causes a delay in the recovery from SPEM to normal glandular composition. HGFA also promotes foveolar cell hyperplasia and mucosal cell proliferation in acute oxyntic injury.
Department of Gastrointestinal Surgery, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
Yukinori
Y
Yamagata
Susumu
S
Aikou
Tsuyoshi
T
Fukushima
Hiroaki
H
Kataoka
Yasuyuki
Y
Seto
Hiroyasu
H
Esumi
Michio
M
Kaminishi
James R
JR
Goldenring
Sachiyo
S
Nomura
D000818:Animals; D001284:Atrophy / Q000378:metabolism; D001384:Azetidines; D005753:Gastric Mucosa / Q000473:pathology; D005755:Gastrins / Q000097:blood*; D006965:Hyperplasia / Q000473:pathology / Q000517:prevention & control*; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D008679:Metaplasia / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D010295:Parietal Cells, Gastric / Q000187:drug effects / Q000473:pathology; D010455:Peptides; D010879:Piperazines; D012697:Serine Endopeptidases / Q000235:genetics*
D001384:Azetidines; D005755:Gastrins; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D010879:Piperazines; C451060:spasmolytic polypeptide; C105999:DMP 777; C081092:HGF activator; D012697:Serine Endopeptidases