title: Loading of mechanical pressure activates mitogen-activated protein kinase and early immediate gene in intestinal epithelial cells.
abstract: 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.
authors.affiliation: Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Hirokawa
authors.forename: S
authors.initials: S
authors.lastname: Miura
authors.forename: H
authors.initials: H
authors.lastname: Kishikawa
authors.forename: H
authors.initials: H
authors.lastname: Yoshida
authors.forename: H
authors.initials: H
authors.lastname: Nakamizo
authors.forename: H
authors.initials: H
authors.lastname: Higuchi
authors.forename: R C
authors.initials: RC
authors.lastname: Nakatsumi
authors.forename: H
authors.initials: H
authors.lastname: Suzuki
authors.forename: H
authors.initials: H
authors.lastname: Saito
authors.forename: H
authors.initials: H
authors.lastname: Ishii
mesh_terms: 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
chemical_list: D018808:Transcription Factor AP-1; D020928:Mitogen-Activated Protein Kinases