Effect and mechanism of H. pylori in regulation of REDD1 expression in gastric mucosa

Objective Regulated in development and DNA damage responses-1 (REDD1) is a conserved and ubiquitous protein, and is induced in response to multiple stimuli. However, its regulation, function and clinical relevance in Helicobacter pylori (H. pylori)-associated gastritis are presently unknown. The stu...

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Main Authors: YAN Zongbao, MAO Fangyuan, SHAN Zhiguo, ZHAO Yongliang, ZHUANG Yuan
Format: Article
Language:zho
Published: Editorial Office of Journal of Third Military Medical University 2022-03-01
Series:Di-san junyi daxue xuebao
Subjects:
Online Access:http://aammt.tmmu.edu.cn/Upload/rhtml/202107181.htm
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author YAN Zongbao
MAO Fangyuan
SHAN Zhiguo
ZHAO Yongliang
ZHUANG Yuan
author_facet YAN Zongbao
MAO Fangyuan
SHAN Zhiguo
ZHAO Yongliang
ZHUANG Yuan
author_sort YAN Zongbao
collection DOAJ
description Objective Regulated in development and DNA damage responses-1 (REDD1) is a conserved and ubiquitous protein, and is induced in response to multiple stimuli. However, its regulation, function and clinical relevance in Helicobacter pylori (H. pylori)-associated gastritis are presently unknown. The study aimed to investigate its expression and regulation mechanism in H. pylori infection. Methods C57 mice and gastric epithelial cells (AGS cells) were respectively infected with H. pylori to establish infected models. Then the expression of REDD1 at mRNA and protein levels was detected by quantitative PCR, immunohistochemical staining and Western blotting. The mechanism of REDD1 up-regulation induced by H. pylori infection was investigated by transfection with signaling pathway inhibitor, plasmid or dual-luciferase reporting analysis in cell models. Results The expression of REDD1 was increased in gastric mucosa of the H. pylori-infected mice than the un-infected ones. Compared with the wild-type strain of H. pylori, the strain with cagA knockout (△cagA H. pylori 11637 cells) showed decreased effect on the upregulation of REDD1 (P < 0.05). H. pylori infection induced up-regulation of REDD1 in AGS cells in a time-, cagA- and pathogen dose-dependent manner (P < 0.05). Blocking of P38/MAPKp38 signaling pathway could significantly inhibit the upregulation of REDD1 induced by the infection (P < 0.05). Conclusion H. pylori induces the up-regulation of REDD1 through activation of phosphorylated cagA in MAPKp38 pathway in the gastric mucosa of mouse with H. pylori infection.
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spelling doaj.art-7d415358f44d4cad93601189aad4d2812022-12-21T19:27:26ZzhoEditorial Office of Journal of Third Military Medical UniversityDi-san junyi daxue xuebao1000-54042022-03-0144541342010.16016/j.2097-0927.202107181Effect and mechanism of H. pylori in regulation of REDD1 expression in gastric mucosaYAN Zongbao0 MAO Fangyuan1SHAN Zhiguo2 ZHAO Yongliang3ZHUANG Yuan4Department of General Surgery, First Affiliated Hospital, Army Medical University (Third Military Medical University), Chongqing, 400038Department of Microbiology and Biochemical Pharmacy, Faculty of Pharmacy and Laboratory Medicine, Army Medical University (Third Military Medical University), Chongqing, 400038, China Department of General Surgery, First Affiliated Hospital, Army Medical University (Third Military Medical University), Chongqing, 400038Department of General Surgery, First Affiliated Hospital, Army Medical University (Third Military Medical University), Chongqing, 400038Department of Microbiology and Biochemical Pharmacy, Faculty of Pharmacy and Laboratory Medicine, Army Medical University (Third Military Medical University), Chongqing, 400038, ChinaObjective Regulated in development and DNA damage responses-1 (REDD1) is a conserved and ubiquitous protein, and is induced in response to multiple stimuli. However, its regulation, function and clinical relevance in Helicobacter pylori (H. pylori)-associated gastritis are presently unknown. The study aimed to investigate its expression and regulation mechanism in H. pylori infection. Methods C57 mice and gastric epithelial cells (AGS cells) were respectively infected with H. pylori to establish infected models. Then the expression of REDD1 at mRNA and protein levels was detected by quantitative PCR, immunohistochemical staining and Western blotting. The mechanism of REDD1 up-regulation induced by H. pylori infection was investigated by transfection with signaling pathway inhibitor, plasmid or dual-luciferase reporting analysis in cell models. Results The expression of REDD1 was increased in gastric mucosa of the H. pylori-infected mice than the un-infected ones. Compared with the wild-type strain of H. pylori, the strain with cagA knockout (△cagA H. pylori 11637 cells) showed decreased effect on the upregulation of REDD1 (P < 0.05). H. pylori infection induced up-regulation of REDD1 in AGS cells in a time-, cagA- and pathogen dose-dependent manner (P < 0.05). Blocking of P38/MAPKp38 signaling pathway could significantly inhibit the upregulation of REDD1 induced by the infection (P < 0.05). Conclusion H. pylori induces the up-regulation of REDD1 through activation of phosphorylated cagA in MAPKp38 pathway in the gastric mucosa of mouse with H. pylori infection. http://aammt.tmmu.edu.cn/Upload/rhtml/202107181.htmhelicobacter pyloriregulated in development and dna damage responses-1mapkp38
spellingShingle YAN Zongbao
MAO Fangyuan
SHAN Zhiguo
ZHAO Yongliang
ZHUANG Yuan
Effect and mechanism of H. pylori in regulation of REDD1 expression in gastric mucosa
Di-san junyi daxue xuebao
helicobacter pylori
regulated in development and dna damage responses-1
mapk
p38
title Effect and mechanism of H. pylori in regulation of REDD1 expression in gastric mucosa
title_full Effect and mechanism of H. pylori in regulation of REDD1 expression in gastric mucosa
title_fullStr Effect and mechanism of H. pylori in regulation of REDD1 expression in gastric mucosa
title_full_unstemmed Effect and mechanism of H. pylori in regulation of REDD1 expression in gastric mucosa
title_short Effect and mechanism of H. pylori in regulation of REDD1 expression in gastric mucosa
title_sort effect and mechanism of h pylori in regulation of redd1 expression in gastric mucosa
topic helicobacter pylori
regulated in development and dna damage responses-1
mapk
p38
url http://aammt.tmmu.edu.cn/Upload/rhtml/202107181.htm
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AT shanzhiguo effectandmechanismofhpyloriinregulationofredd1expressioningastricmucosa
AT zhaoyongliang effectandmechanismofhpyloriinregulationofredd1expressioningastricmucosa
AT zhuangyuan effectandmechanismofhpyloriinregulationofredd1expressioningastricmucosa