title: CagA promotes proliferation and secretion of extracellular matrix by inhibiting signaling pathway of apoptosis in rat glomerular mesangial cells.
abstract: Cytotoxin-associated antigen A (CagA), a major virulence factor of Helicobacter pylori (Hp), is associated with the pathogenesis of peptic ulcer and gastric cancer. Recent researches demonstrated that Hp exists in palatine tonsil in all studied IgA nephropathy (IgAN) patients, most of which were CagA-positive, suggesting that CagA may be a causative pathogenic factor of IgAN. However, the underlying molecular mechanisms and signaling pathway are still largely unclear. In the present study, CCK8 assay, enzyme-linked immunosorbent assay, and immunohistochemistry were performed to investigate the effect of CagA on cell proliferation and extracellular matrix secretion in rat glomerular mesangial cells. RT-PCR and western blotting were used to reveal the potential signaling pathway. Rat glomerular mesangial cells were treated with recombinant CagA protein for 72 h, in a dose- and time-dependent manner. We found that CagA promoted cell proliferation and extracellular matrix secretion by inhibiting signaling pathway of apoptosis. Taken together, these findings suggested that CagA induced cellular injury in glomerular mesangium by proliferation and secretion of extracellular matrix, and may play an important role in pathogenesis of IgAN.
authors.affiliation: a Research Center of Combine Traditional Chinese and Western Medicine, Affiliated Traditional Medicine Hospital , Sichuan Medical University , Luzhou , Sichuan , China ;
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: a Research Center of Combine Traditional Chinese and Western Medicine, Affiliated Traditional Medicine Hospital , Sichuan Medical University , Luzhou , Sichuan , China ;
authors.forename: Rui-Zhi
authors.initials: RZ
authors.lastname: Tan
authors.affiliation: b Department of Nephrology , The First People's Hospital of Zigong , Zigong , Sichuan , China ;
authors.forename: Yue
authors.initials: Y
authors.lastname: Chen
authors.affiliation: a Research Center of Combine Traditional Chinese and Western Medicine, Affiliated Traditional Medicine Hospital , Sichuan Medical University , Luzhou , Sichuan , China ;
authors.forename: Hong-Lian
authors.initials: HL
authors.lastname: Wang
authors.affiliation: a Research Center of Combine Traditional Chinese and Western Medicine, Affiliated Traditional Medicine Hospital , Sichuan Medical University , Luzhou , Sichuan , China ;
authors.forename: Yu-Hang
authors.initials: YH
authors.lastname: Liu
authors.affiliation: c College of Clinical Medical , Sichuan Medical University , Luzhou , Sichuan , China ;
authors.forename: Dan
authors.initials: D
authors.lastname: Wen
authors.affiliation: d Department of Nephrology , The Affiliated Hospital of Sichuan Medical University , Luzhou , Sichuan , China ;|e State Key Laboratory of Biotherapy of Human Disease, West China Hospital , Sichuan University , Chengdu , Sichuan , China.
authors.forename: Jun-Ming
authors.initials: JM
authors.lastname: Fan
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000494:pharmacology*; D017209:Apoptosis; D001426:Bacterial Proteins / Q000494:pharmacology*; D018929:Cell Culture Techniques; D002460:Cell Line; D049109:Cell Proliferation; D005109:Extracellular Matrix / Q000378:metabolism*; D005920:Glomerular Mesangium / Q000166:cytology*; D005922:Glomerulonephritis, IGA / Q000503:physiopathology; D051381:Rats; D015398:Signal Transduction
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C080866:cagA protein, Helicobacter pylori
keywords: CagA; IgAN; extracellular matrix; glomerular mesangium; proliferation