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

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.

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.

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).

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.