H. pylori infection induced BMAL1 expression and rhythm disorder aggravate gastric inflammation

Background: Rhythm abnormalities are crucial for diverse diseases. However, their role in diseasegress n induced by Helicobacter pylori (II pylori) remains elusive. Methods: IL pylori infection was used in in vivo and in vitro experiments to examine its effect on rhythmic genes. The GEO database was used to screen /I. pylori affecting rhythm genes, and the effect of rhythm genes on inflammatory factors. Chromatin immunoprecipitation and dual luciferase assays were used to further find out the regulation between molecules. Animal models were used to confirm the relationship between rhythm genes and H. pylori-induced inflammation. Findings: BMALI disorders aggravate inflammation induced by H. pylori. Specifically, H. pylori induce BMALI expression in vitro and in vivo through transcriptional activation of LIN28A, breaking the circadian rhythm. Mechanistically, LIN28A binds to the promoter region of BMALI and directly activates its transcription under H. pylon infection. BMALI in turn functions as a transcription factor and enhances the expression of proinflammatory cytokine TNF-alpha, thereby promoting inflammation. Of note, BMALI dysfunction in the rhythm disorder animal model aggravates inflammatory response induced by H. pylori infection in vivo. Interpretation: These findings in this study imply the pathogenic relationship between BMALI and H. pyloH. BMALI may serve as a potential diagnostic marker and therapeutic target for the early diagnosis and treatment of diseases related toll. pylon infection. Fund: National Natural Science Foundation of China. (C) 2018 The Authors. Published by Elsevier B.V.