Helicobacter pylori cytotoxin-associated gene A impaires the filtration barrier function of podocytes via p38 MAPK signal pathway
Helicobacter pylori (Hp) specific antigens were found deposited in the glomeruli in some kidney diseases. However, the underlying molecular mechanisms remain to be elucidated. This study was to investigate the effect of cytotoxin associated gene A protein (CagA), a key virulence factor of Hp, on mouse podocytes. Cells were cultured and treated with recombinant CagA protein. The expression of the tight junction protein ZO-1 and p38 MAPK signal pathway were measured by real-time RT-PCR and western blotting. The filtration barrier function of podocytes was evaluated by albumin influx assay. CagA decreased the expression and membrane distribution of ZO-1, impaired the filtration barrier function of podocytes, while activating p38 MAPK signal pathway in these cells. Selective p38 MAPK inhibition partly prevented CagA-induced filtration barrier dysfunction of podocytes through ameliorating ZO-1 downregulation. Taken together, the results suggested that CagA, at least via p38 MAPK signal pathway, may induce podocyte injury. Anti-Hp therapy may be beneficial for the treatment of kidney diseases related to Hp antigen deposition.
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