The Institute of Medical Science, The University Of Tokyo

  1. Home
  2. Scientific Papers

Scientific Papers/Award

Helicobacter pylori Dampens Gut Epithelial Self-Renewal by Inhibiting Apoptosis, a Bacterial Strategy to Enhance Colonization of the Stomach

Cell Host and Microbe 2, 250-263, 2007
Hitomi Mimuro, Toshihiko Suzuki, Shigenori Nagai, Gabriele Rieder, Masato Suzuki, Takeshi Nagai, Yukihiro Fujita, Kanna Nagamatsu, Nozomi Ishijima, Shigeo Koyasu, Rainer Haas, and Chihiro Sasakawa.
Department of Microbiology and Immunology, International Research Center for Infectious Diseases

Colonization of the gastric pits in the stomach by Helicobacter pylori (Hp) is a major risk factor for gastritis, gastric ulcers, and cancer. Normally, rapid self-renewal of gut epithelia, which occurs by a balance of progenitor proliferation and pit cell apoptosis, serves as a host defense mechanism to limit bacterial colonization. To investigate how Hp overcomes this host defense, we use the Mongolian gerbil model of Hp infection. Apoptotic loss of pit cells induced by a proapoptotic agent is suppressed by Hp. The ability of Hp to suppress apoptosis contributed to pit hyperplasia and persistent bacterial colonization of the stomach. Infection with WT Hp but not with a mutant in the virulence effector cagA increased levels of the prosurvival factor phospho-ERK and antiapoptotic protein MCL1 in the gastric pits. Thus, CagA activates host cell survival and antiapoptotic pathways to overcome self-renewal of the gastric epithelium and help sustain Hp infection.