PUMA-mediated epithelial cell apoptosis promotes Helicobacter pylori infection-mediated gastritis
Open Access
- 20 February 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Cell Death & Disease
- Vol. 11 (2), 1-10
- https://doi.org/10.1038/s41419-020-2339-x
Abstract
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-κB p65 binds to PUMA promoter to activate PUMA transcription after H. pylori infection. In addition, NF-κB 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-κB-mediated transcriptional regulation of PUMA contributes to the pathogenesis of H. pylori-infected gastritis.Keywords
Funding Information
- National Natural Science Foundation of China (81302109, 81502611)
This publication has 40 references indexed in Scilit:
- PUMA-mediated intestinal epithelial apoptosis contributes to ulcerative colitis in humans and miceJCI Insight, 2011
- Transmission pathway of Helicobacter pylori: Does food play a role in rural and urban areas?International Journal of Food Microbiology, 2010
- The many roads traveled byHelicobacter pylorito NF-κB activationGut Microbes, 2010
- Helicobacter pylori CagA activates NF‐κB by targeting TAK1 for TRAF6‐mediated Lys 63 ubiquitinationEMBO Reports, 2009
- PUMA is directly activated by NF-κB and contributes to TNF-α-induced apoptosisCell Death & Differentiation, 2009
- PUMA, a potent killer with or without p53Oncogene, 2008
- PUMA Regulates Intestinal Progenitor Cell Radiosensitivity and Gastrointestinal SyndromeCell Stem Cell, 2008
- p53 independent induction of PUMA mediates intestinal apoptosis in response to ischaemia-reperfusionGut, 2007
- Deficiencies of Myeloid Differentiation Factor 88, Toll-Like Receptor 2 (TLR2), or TLR4 Produce Specific Defects in Macrophage Cytokine Secretion Induced byHelicobacter pyloriInfection and Immunity, 2007
- The NF-κB regulator Bcl-3 and the BH3-only proteins Bim and Puma control the death of activated T cellsProceedings of the National Academy of Sciences of the United States of America, 2006