Role of Outer Inflammatory Protein A/Cystine-Glutamate Transporter Pathway in Gastric Mucosa Injury Induced by <i>Helicobacter pylori</i>

Abstract

Background: Helicobacter pylori (Hp) infection is a major cause of gastrointestinal disease. However, the pathogenesis of gastric mucosa injury by Hp remains unclear. Our previous research has been shown that aspirin-induced gastric injury was associated with reduction of glutamate release by inhibiting cystine-glutamate transporter (xCT) activity. It's likely that the xCT pathway may be involved in Hp-induced gastric mucosa injury. Methods: In the Hp-infected animals, cell lines and patients, the activity of xCT and the regulatory effect of miRNA on xCT were tested, and the effect of OipA from Hp on xCT activity was observed. Findings: In vivo and vitro experiments, Hp infection induced gastric mucosa injury with a reduction of xCT, which was attenuated by exogenous glutamate treatment. The expression of miR-30b and miR-27a was up-regulated, and miR-30b/27a inhibitors significantly attenuated gastric mucosa injury and reduction of xCT activity by Hp infection. Furthermore, the outer inflammatory protein A (OipA), a virulence protein from Hp, significantly up-regulated the expression of miR-30b and decreased the activity of xCT. These results suggested that micro30b/xCT mediated OipA plays a significant role in gastric mucosa injury induced by Hp. Interpretation: OipA is one of classical virulence protein from Hp, which promotes inflammatory cytokines secretion and heightens gastric inflammation. In our study, the effect of OipA on the microRNA/glutamate pathway in Hp-induced mucosa injury was observed. Glutamate has exhibited protective effect on gastric ulcer. Thus, OipA, besides promotive effect of gastric mucosa injury (promoting inflammation), may attenuate protective effect of gastric tissue itself on damage (inhibiting glutamate activity). Funding Statement: This work was supported by the National Natural Science Foundation of China (No. 81573486 to Yuan-Jian Li, No. 81703592 to Jie Du, No. 81770739 to Zhi-Cheng Gong). It is also supported by the Open Sharing Fund for the Large-scale Instruments and Equipments of Central South University. Declaration of Interests: The authors declare they have no conflict of interests. Ethics Approval Statement: All protocols of animal experiments were approved by the Central South University Veterinary Medicine Animal Care and Use Committee and all procedures were performed according to the National Institutes of Health Guide for the Care and Use of Laboratory Animals. Clinical research project was approved by the Third Xiangya Hospital, Hunan, China (approval number: 2015-S109).