title: Upregulation of progranulin by Helicobacter pylori in human gastric epithelial cells via p38MAPK and MEK1/2 signaling pathway: role in epithelial cell proliferation and migration.
abstract: Helicobacter pylori is a major human pathogen associated with gastric diseases such as chronic active gastritis, peptic ulcer, and gastric carcinoma. The growth factor progranulin (PGRN) is a secreted glycoprotein that functions as an important regulator of cell growth, migration, and transformation. We aimed to determine the molecular mechanisms by which H. pylori upregulates the expression of PGRN and the relationship between H. pylori infection and production of PGRN in controlling cell proliferation and migration. Levels of PGRN were examined in gastric tissues from patients and in vitro in gastric epithelial cells. Cell proliferation was measured by colony formation assay. Cell migration was monitored by wound healing migration assay. PGRN protein levels were increased in patients with gastritis and gastric cancer tissue. Infection of gastric epithelial cells with H. pylori significantly increased PGRN expression in a time-dependent manner. Blockade of the p38 and MEK1/2 pathway by inhibitor inhibited H. pylori-mediated PGRN upregulation. Activation of p38 and MEK1/2 pathway by H. pylori was also identified. Knockdown of PGRN attenuated the H. pylori-induced proliferative activity and migration of cancer cells. These findings suggest that the upregulation of PGRN in H. pylori-infected gastric epithelial cells may contribute to the carcinogenic process.
authors.affiliation: Department of Microbiology, Key Laboratory for Experimental Teratology of Chinese Ministry of Education, School of Medicine, Shandong University, Jinan, Shandong, China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Wang
authors.forename: Yundong
authors.initials: Y
authors.lastname: Sun
authors.forename: Shili
authors.initials: S
authors.lastname: Liu
authors.forename: Han
authors.initials: H
authors.lastname: Yu
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Li
authors.forename: Jiping
authors.initials: J
authors.lastname: Zeng
authors.forename: Chunyan
authors.initials: C
authors.lastname: Chen
authors.forename: Jihui
authors.initials: J
authors.lastname: Jia
mesh_terms: D054443:Cell Migration Assays; D002465:Cell Movement; D049109:Cell Proliferation; D003114:Colony-Forming Units Assay; D004847:Epithelial Cells / Q000382:microbiology*; D005753:Gastric Mucosa / Q000473:pathology; D020869:Gene Expression Profiling; D016480:Helicobacter pylori / Q000472:pathogenicity*; D054884:Host-Pathogen Interactions; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis*; D048369:MAP Kinase Kinase 1 / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D000077153:Progranulins; D015398:Signal Transduction; D015854:Up-Regulation; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: C492314:GRN protein, human; D036341:Intercellular Signaling Peptides and Proteins; D000077153:Progranulins; D048051:p38 Mitogen-Activated Protein Kinases; D048369:MAP Kinase Kinase 1; C482125:MAP2K1 protein, human