Helicobacter pylori dampens gut epithelial self-renewal by inhibiting apoptosis, a bacterial strategy to enhance colonization of the stomach
Helicobacter pylori dampens gut epithelial self-renewal by inhibiting apoptosis, a bacterial strategy to enhance colonization of the stomach
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DOI：
10.1016/j.chom.2007.09.005
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发表时间：
2007-10-01
影响因子：
30.3
通讯作者：
Sasakawa, Chihiro
中科院分区：
文献类型：
--
作者：
Mimuro, Hitomi;Suzuki, Toshihiko;Sasakawa, Chihiro
幽门螺杆菌（Hp）在胃中胃小凹的定植是胃炎、胃溃疡和癌症的主要危险因素。通常，通过祖细胞增殖和小凹细胞凋亡的平衡而发生的肠上皮细胞的快速自我更新充当限制细菌定植的宿主防御机制。为了研究Hp如何克服这种宿主防御，我们使用蒙古沙鼠Hp感染模型。幽门螺杆菌可抑制由促凋亡剂诱导的小凹细胞凋亡损失。幽门螺杆菌抑制细胞凋亡的能力有助于胃小凹增生和持续的细菌定植。感染野生型Hp，但不与突变体的毒力效应cagA增加水平的促生存因子磷酸化ERK和抗凋亡蛋白MCL1在胃小凹。因此，CagA激活宿主细胞存活和抗凋亡途径，以克服胃上皮的自我更新，并帮助维持Hp感染。
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.