PMID- 25867766
OWN - NLM
STAT- MEDLINE
DCOM- 20150825
LR  - 20230216
IS  - 1530-0307 (Electronic)
IS  - 0023-6837 (Linking)
VI  - 95
IP  - 6
DP  - 2015 Jun
TI  - Osteopontin depletion decreases inflammation and gastric epithelial proliferation 
      during Helicobacter pylori infection in mice.
PG  - 660-71
LID - 10.1038/labinvest.2015.47 [doi]
AB  - 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.
FAU - Park, Jun Won
AU  - Park JW
AD  - 1] Department of Veterinary Pathology, College of Veterinary Medicine, Seoul 
      National University, Seoul, Korea [2] National Cancer Center, Goyang, Gyeonggi, 
      Korea.
FAU - Lee, Su Hyung
AU  - Lee SH
AD  - Department of Veterinary Pathology, College of Veterinary Medicine, Seoul 
      National University, Seoul, Korea.
FAU - Go, Du Min
AU  - Go du M
AD  - Department of Veterinary Pathology, College of Veterinary Medicine, Seoul 
      National University, Seoul, Korea.
FAU - Kim, Hark Kyun
AU  - Kim HK
AD  - National Cancer Center, Goyang, Gyeonggi, Korea.
FAU - Kwon, Hyo-Jung
AU  - Kwon HJ
AD  - College of Veterinary Medicine, Chungnam National University, Daejeon, Korea.
FAU - Kim, Dae-Yong
AU  - Kim DY
AD  - Department of Veterinary Pathology, College of Veterinary Medicine, Seoul 
      National University, Seoul, Korea.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150413
PL  - United States
TA  - Lab Invest
JT  - Laboratory investigation; a journal of technical methods and pathology
JID - 0376617
RN  - 0 (Cytokines)
RN  - 0 (Spp1 protein, mouse)
RN  - 106441-73-0 (Osteopontin)
SB  - IM
MH  - Animals
MH  - Cell Line, Tumor
MH  - Cell Proliferation/*physiology
MH  - Cytokines
MH  - Female
MH  - Gastric Mucosa/*metabolism
MH  - Gene Knockout Techniques
MH  - Helicobacter Infections/*metabolism
MH  - Helicobacter pylori
MH  - Humans
MH  - Inflammation/*metabolism
MH  - Macrophages
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Osteopontin/genetics/*metabolism
MH  - Up-Regulation
EDAT- 2015/04/14 06:00
MHDA- 2015/08/26 06:00
CRDT- 2015/04/14 06:00
PHST- 2014/08/18 00:00 [received]
PHST- 2015/01/22 00:00 [revised]
PHST- 2015/01/28 00:00 [accepted]
PHST- 2015/04/14 06:00 [entrez]
PHST- 2015/04/14 06:00 [pubmed]
PHST- 2015/08/26 06:00 [medline]
AID - S0023-6837(22)02333-9 [pii]
AID - 10.1038/labinvest.2015.47 [doi]
PST - ppublish
SO  - Lab Invest. 2015 Jun;95(6):660-71. doi: 10.1038/labinvest.2015.47. Epub 2015 Apr 
      13.