| First Author | Park JW | Year | 2015 |
| Journal | Lab Invest | Volume | 95 |
| Issue | 6 | Pages | 660-71 |
| PubMed ID | 25867766 | Mgi Jnum | J:222619 |
| Mgi Id | MGI:5645145 | Doi | 10.1038/labinvest.2015.47 |
| Citation | Park JW, et al. (2015) Osteopontin depletion decreases inflammation and gastric epithelial proliferation during Helicobacter pylori infection in mice. Lab Invest 95(6):660-71 |
| abstractText | Osteopontin (OPN) is a multifunctional protein that plays a role in many physiological and pathological processes, including inflammation and tumorigenesis. Here, we investigated the involvement of OPN in Helicobacter pylori (HP)-induced gastritis using OPN knockout (KO) mice and OPN knockdown (KD) cell lines. HP-infected OPN KO mice showed significantly reduced gastritis compared with wild-type (WT) mice with decreased infiltration of macrophages and a reduction in HP-induced upregulation of IL-1beta, TNF-alpha, and IFN-gamma. HP-exposed OPN KD gastric cancer cells and macrophage-like cells showed an attenuated induction of these cytokines. We also demonstrated a reduction in the migration of monocytic and macrophage-like cells toward conditioned media harvested from HP-exposed OPN KD gastric cancer cells as well as reduced migration ability of OPN KD cells itself. In addition, HP-infected OPN KO mice showed decreased epithelial cell proliferation compared with HP-infected WT mice, in association with a reduction in MAPK pathway activation. OPN KD gastric cancer cell lines also showed lower proliferative activity and reduced MAPK activation than shRNA control cells after HP co-culture or after IL-1beta and TNF-alpha treatment. Taken together, these results indicate that OPN exerts a considerable influence on HP-induced gastritis by modulating the production of cytokines and contributing to macrophage infiltration. Moreover, OPN-mediated activation of the MAPK pathway in gastric epithelial cells might contribute to epithelial changes following HP infection. |
