CagA, a major virulence factor of Helicobacter pylori, promotes the production and underglycosylation of IgA1 in DAKIKI cells.
While Helicobacter pylori (Hp) infection is closely associated with IgA nephropathy (IgAN), the underlying molecular mechanisms remain to be elucidated. This study was to investigate the effect of cytotoxin associated gene A protein (CagA), a major virulence factor of Hp, on the production and underglycosylation of IgA1 in the B cell line DAKIKI cells. Cells were cultured and treated with recombinant CagA protein. We found that CagA stimulated cell proliferation and the production of IgA1 in a dose-dependent and time-dependent manner. Moreover, CagA promoted the underglycosylation of IgA1, which at least partly attributed to the downregulation of β1,3-galactosyltransferase (C1GALT1) and its chaperone Cosmc. In conclusion, we demonstrated that Hp infection, at least via CagA, may participate in the pathogenesis of IgAN by influencing the production and glycosylation of IgA1 in B cells.
Department of Nephrology, The First Affiliated Hospital of Chengdu Medical College, Chengdu City 610500, China.
Man
M
Yang
Department of Nephrology, Affiliated Hospital of Luzhou Medical College, Luzhou City 646000, China.
Fu-gang
FG
Li
Department of Nephrology, Second Clinical Medical Institution of North Sichuan Medical College (Nanchong Central Hospital), Nanchong City 637400, China.
Xi-sheng
XS
Xie
Department of Nephrology, The First Affiliated Hospital of Chengdu Medical College, Chengdu City 610500, China.
Shao-qing
SQ
Wang
Department of Nephrology, The First Affiliated Hospital of Chengdu Medical College, Chengdu City 610500, China; Department of Nephrology, Affiliated Hospital of Luzhou Medical College, Luzhou City 646000, China. Electronic address: junmingfan@163.com.
Jun-ming
JM
Fan
D000942:Antigens, Bacterial / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D001402:B-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005700:Galactosyltransferases / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D005922:Glomerulonephritis, IGA / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D006031:Glycosylation / Q000187:drug effects; D016481:Helicobacter Infections / Q000150:complications / Q000382:microbiology; D016480:Helicobacter pylori / Q000502:physiology; D054884:Host-Pathogen Interactions; D006801:Humans; D007070:Immunoglobulin A / Q000378:metabolism*; D018832:Molecular Chaperones / Q000235:genetics; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C505369:C1GALT1C1 protein, human; D007070:Immunoglobulin A; D018832:Molecular Chaperones; D011994:Recombinant Proteins; C080866:cagA protein, Helicobacter pylori; C505293:C1GALT1 protein, human; D005700:Galactosyltransferases
Cytotoxin associated gene A protein; IgA nephropathy; IgA1; Underglycosylation