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Helicobacter pylori inhibits autophagic flux and promotes its intracellular survival and colonization by down-regulating SIRT1 |
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| Authors: | Xin Wang Bo Wang Wei Gao Yifei An Guoying Dong Jihui Jia Qing Yang |
| Affiliation: | 1. Institute of Pathogen Biology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China Contribution: Conceptualization (supporting), Formal analysis (equal), Investigation (lead), Methodology (lead);2. Department of Traditional Medicine, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China Contribution: Conceptualization (supporting), Funding acquisition (supporting), Investigation (supporting), Methodology (supporting);3. Department of Pathology, Jinan Central Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China Contribution: Investigation (supporting), Methodology (supporting);4. Institute of Pathogen Biology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China Contribution: Investigation (supporting), Methodology (supporting);5. Institute of Pathogen Biology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China Key Laboratory for Experimental Teratology of Ministry of Education, Shandong University, Jinan, China Shandong Key Laboratory of Infection and Immunity, Shandong University, Jinan, China Karolinska Institute Collaborative Laboratory for Cancer research, Shandong University, Jinan, China Contribution: Conceptualization (supporting), Formal analysis (supporting), Funding acquisition (supporting), Writing - original draft (supporting);6. Institute of Pathogen Biology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China |
| Abstract: | Helicobacter pylori (H. pylori) is the strong risk factor for a series of gastric pathological changes. Persistent colonization of H. pylori leading to chronic infection is responsible for gastritis and malignancy. Autophagy is an evolutionary conserved process which can protect cells and organisms from bacterial infection. Here, we demonstrated that H. pylori infection induced autophagosome formation but inhibited autophagic flux. SIRT1, a class III histone deacetylase, was down-regulated at both mRNA and protein levels by H. pylori infection in gastric cells. Further investigation showed that the transcriptional factor RUNX3 accounted for down-regulation of SIRT1 in H. pylori-infected gastric cells. SIRT1 promoted autophagic flux in gastric cells and activation of SIRT1 restored the autophagic flux inhibited by H. pylori infection. Furthermore, SIRT1 exerted inhibitory effects on intracellular survival and colonization of H. pylori. And activation of autophagic flux in SIRT1-inhibited gastric cells could significantly reduce intracellular load of H. pylori. Moreover, the relationship between H. pylori infection and SIRT1 expression was identified in clinical specimen. Our findings define the importance of SIRT1 in compromised autophagy induced by H. pylori infection and bacterial intracellular colonization. These results provide evidence that SIRT1 can serve as a therapeutic target to eradicate H. pylori infection. |
| Keywords: | autophagic flux autophagosome Helicobacter pylori intracellular colonization intracellular survival SIRT1 |