Transmural pressure loading enhances gastric mucosal cell proliferation.
OBJECTIVE
Although increased intraluminal pressure in the stomach due to gastric outlet obstruction or functional gastric motor dysfunction, including gastroparesis, may affect gastric mucosal integrity, the direct effect of mechanical pressure on gastric mucosal cells has not yet been fully investigated. The aims of this study were to determine whether exposure to transmural pressure would affect the proliferation of gastric mucosal cells and to elucidate the intracellular signaling pathways involved.


METHODS
Cellular proliferation and DNA synthesis were evaluated in rat gastric epithelial cells exposed to high transmural pressures. The levels of activation of 3 MAP kinases, ERK, JNK, and p38, were assessed, and the induction of immediate early gene expression was examined. The activation of nuclear factor activator protein-1 (AP-1) was evaluated by an electrophoretic mobility shift assay.


RESULTS
Exposure to high transmural pressure significantly increased DNA synthesis within 24 h, with the most marked increase observed after exposure to a pressure of 80 mmHg, and this increase was inhibited by the MEK1 inhibitor PD98059. Early activation of ERK kinase, but not of JNK or p38 kinase, was detected after pressure loading. Early induction of the c-fos and c-myc genes and activation of the AP-1 transcription factor were also demonstrated within 3 h of exposure to 80 mmHg of pressure.


CONCLUSIONS
Gastric mucosal cell proliferation induced by exposure to high transmural pressure may be related to early activation of ERK, the induction of c-fos and c-myc, and the activation of AP-1.
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Hiromasa
H
Nakamizo
Hidekazu
H
Suzuki
Soichiro
S
Miura
Sachiko
S
Mogami
Hiroshi
H
Kishikawa
Hideo
H
Yoshida
Hirofumi
H
Matsui
Toshifumi
T
Hibi
D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation; D004247:DNA / Q000096:biosynthesis / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D005753:Gastric Mucosa / Q000166:cytology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism; D020929:Mitogen-Activated Protein Kinase Kinases / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D011312:Pressure; D011485:Protein Binding; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism
D005419:Flavonoids; D017874:Immediate-Early Proteins; D016760:Proto-Oncogene Proteins c-fos; D016271:Proto-Oncogene Proteins c-myc; D018808:Transcription Factor AP-1; D004247:DNA; D020929:Mitogen-Activated Protein Kinase Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one