PUMA-mediated epithelial cell apoptosis promotes Helicobacter pylori infection-mediated gastritis

被引:21
|
作者
Dang, Yini [1 ]
Zhang, Yifeng [2 ]
Xu, Lingyan [3 ]
Zhou, Xiaoying [1 ]
Gu, Yanhong [3 ]
Yu, Jian [4 ]
Jin, Shidai [3 ]
Ji, Haoming [5 ]
Shu, Yongqian [3 ]
Zhang, Guoxin [1 ]
Cui, Shiyun [3 ]
Sun, Jing [3 ]
机构
[1] Nanjing Med Univ, Dept Gastroenterol, Affiliated Hosp 1, Nanjing 210029, Peoples R China
[2] Nanjing Med Univ, Dept Gastroenterol, Nanjing Hosp 1, Nanjing 210001, Peoples R China
[3] Nanjing Med Univ, Dept Oncol, Affiliated Hosp 1, Nanjing 210029, Peoples R China
[4] Univ Pittsburgh, Sch Med, Dept Pathol & Radiat Oncol, Pittsburgh, PA 15213 USA
[5] Haian Peoples Hosp, Dept Oncol, Nantong 226630, Peoples R China
基金
中国国家自然科学基金;
关键词
NF-KAPPA-B; CANCER; P53; CONTRIBUTES; INHIBITION; EXPRESSION; SECRETION; RECEPTOR; PATHWAY; COMPLEX;
D O I
10.1038/s41419-020-2339-x
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The molecular mechanism responsible for Helicobacter pylori infection-mediated gastritis and carcinogenesis is not yet clear. Increased evidence suggests that chronic gastritis and elevated gastric epithelial cell (GEC) apoptosis are crucial events during stomach carcinoma transformation. PUMA is a potent proapoptotic Bcl-2 protein and mediates acute tissue injury. In this study, we aimed to investigate the role of PUMA in GEC apoptosis and inflammation induced by H. pylori infection. As a result, we found that PUMA expression was elevated in gastritis tissues compared with uninvolved tissues, and it was correlated with the severity of apoptosis and gastritis. In mice, PUMA mRNA and protein were markedly induced in GECs upon induction of gastritis by H. pylori. PUMA-deficient mice were highly resistant to apoptosis and gastritis induced by H. pylori. Furthermore, the transcription factor NF-kappa B p65 binds to PUMA promoter to activate PUMA transcription after H. pylori infection. In addition, NF-kappa B inhibitor could rescue H. pylori-induced apoptosis and gastritis. Finally, H. pylori-induced activation of p-p65 and PUMA was mediated via Toll-like receptor 2 (TLR2) and blocked in TLR2 knockout mice. Taken together, these results verified the pro-inflammatory effect of PUMA in H. pylori-infected gastric tissue. Moreover, TLR2/NF-kappa B-mediated transcriptional regulation of PUMA contributes to the pathogenesis of H. pylori-infected gastritis.
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页数:10
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