Loading of mechanical pressure activates mitogen-activated protein kinase and early immediate gene in intestinal epithelial cells.
Intestinal mucosa is continuously exposed to mechanical forces. We examined whether pressure loading activates mitogen-activated protein kinase (MAPK) and expression of early immediate genes in intestinal epithelial cells. Pressure was applied to IEC18 cells by helium gas in a culture flask and pressure-induced cell proliferation was examined. The expression of early immediate genes, MAPK activity, and activation of nuclear factor activator protein-1 (AP-1) were also examined. Pressures significantly promoted cell proliferation with peak effect at 80 mm Hg. Pretreatment with either a protein kinase C inhibitor or tyrosine kinase inhibitors, but not calcium chelating agents significantly inhibited cell proliferation promoted by pressure. Early inductions of c-myc and c-fos proteins, increased activity of MAPK, and activation of AP-1 were observed by pressure loading. Our study showed that intestinal mucosal cell proliferation is promoted by mechanical pressure and various intracellular signaling pathways are involved in the process.
Hirokawa
M
M
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
Miura
S
S
Kishikawa
H
H
Yoshida
H
H
Nakamizo
H
H
Higuchi
H
H
Nakatsumi
R C
RC
Suzuki
H
H
Saito
H
H
Ishii
H
H
D000818:Animals; D015153:Blotting, Western; D002455:Cell Division; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000378:metabolism*; D017781:Genes, Immediate-Early / Q000502:physiology*; D007413:Intestinal Mucosa / Q000166:cytology / Q000502:physiology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D011312:Pressure; D051381:Rats; D015398:Signal Transduction / Q000502:physiology*; D013314:Stress, Mechanical; D018808:Transcription Factor AP-1 / Q000378:metabolism
D018808:Transcription Factor AP-1; D020928:Mitogen-Activated Protein Kinases