title: Helicobacter pylori disrupts host cell membranes, initiating a repair response and cell proliferation.
abstract: Helicobacter pylori (H. pylori), the human stomach pathogen, lives on the inner surface of the stomach and causes chronic gastritis, peptic ulcer, and gastric cancer. Plasma membrane repair response is a matter of life and death for human cells against physical and biological damage. We here test the hypothesis that H. pylori also causes plasma membrane disruption injury, and that not only a membrane repair response but also a cell proliferation response are thereby activated. Vacuolating cytotoxin A (VacA) and cytotoxin-associated gene A (CagA) have been considered to be major H. pylori virulence factors. Gastric cancer cells were infected with H. pylori wild type (vacA+/cagA+), single mutant (ΔvacA or ΔcagA) or double mutant (ΔvacA/ΔcagA) strains and plasma membrane disruption events and consequent activation of membrane repair components monitored. H. pylori disrupts the host cell plasma membrane, allowing localized dye and extracellular Ca(2+) influx. Ca(2+)-triggered members of the annexin family, A1 and A4, translocate, in response to injury, to the plasma membrane, and cell surface expression of an exocytotic maker of repair, LAMP-2, increases. Additional forms of plasma membrane disruption, unrelated to H. pylori exposure, also promote host cell proliferation. We propose that H. pylori activation of a plasma membrane repair is pro-proliferative. This study might therefore provide new insight into potential mechanisms of H. pylori-induced gastric carcinogenesis.
authors.affiliation: Institute of Molecular and Cellular Biology and Department of Life Science, National Taiwan University, Taipei 106, Taiwan.
authors.forename: Li-Ling
authors.initials: LL
authors.lastname: Lin
authors.affiliation: Institute of Biomedical Informatics, Center for Systems and Synthetic Biology, National Yang-Ming University, Taipei 112, Taiwan.
authors.forename: Hsuan-Cheng
authors.initials: HC
authors.lastname: Huang
authors.affiliation: Biological Science, Graduate School of Science, Osaka University, Osaka 560-0043, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ogihara
authors.affiliation: Department of Microbiology, National Taiwan University College of Medicine, Taipei 100, Taiwan.
authors.forename: Jin-Town
authors.initials: JT
authors.lastname: Wang
authors.affiliation: Department of Microbiology, National Taiwan University College of Medicine, Taipei 100, Taiwan.
authors.forename: Meng-Chuan
authors.initials: MC
authors.lastname: Wu
authors.affiliation: Department of Cellular Biology and Anatomy and Institute of Molecular Medicine and Genetics, Georgia Health Science University, 1120 15th St., Augusta, GA 30912, USA.
authors.forename: Paul L
authors.initials: PL
authors.lastname: McNeil
authors.affiliation: Angiogenesis Research Center, National Taiwan University, Taipei 106, Taiwan.|Department of Surgery, National Taiwan University Hospital, Taipei 100, Taiwan.
authors.forename: Chiung-Nien
authors.initials: CN
authors.lastname: Chen
authors.affiliation: Institute of Molecular and Cellular Biology and Department of Life Science, National Taiwan University, Taipei 106, Taiwan.
authors.forename: Hsueh-Fen
authors.identifier: 0000-0003-4876-3309
authors.initials: HF
authors.lastname: Juan
mesh_terms: D000230:Adenocarcinoma / Q000382:microbiology / Q000473:pathology*; D000942:Antigens, Bacterial / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000473:pathology*; D049109:Cell Proliferation; D005434:Flow Cytometry; D016481:Helicobacter Infections / Q000382:microbiology / Q000473:pathology*; D016480:Helicobacter pylori / Q000472:pathogenicity*; D006801:Humans; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000382:microbiology / Q000473:pathology*; D014407:Tumor Cells, Cultured
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D012333:RNA, Messenger; C074689:VacA protein, Helicobacter pylori; C080866:cagA protein, Helicobacter pylori; D002118:Calcium