PMID- 25332857
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20141021
LR  - 20211021
IS  - 2193-1801 (Print)
IS  - 2193-1801 (Electronic)
IS  - 2193-1801 (Linking)
VI  - 3
DP  - 2014
TI  - Differential regulation of c-Met signaling pathways for synovial cell function.
PG  - 554
LID - 10.1186/2193-1801-3-554 [doi]
LID - 554
AB  - We previously demonstrated that blocking the hepatocyte growth factor (HGF) 
      receptor, c-Met, using a HGF antagonist, NK4, inhibited arthritis in a rheumatoid 
      arthritis (RA) model mice. In the present study, we investigated the role of 
      c-Met signaling in synovial cell function. We demonstrated that synovial tissues 
      from RA patients and MH7A cells, a human RA synovial cell line, expressed HGF and 
      c-Met. HGF and c-Met expression in RA synovium was increased compared to 
      osteoarthritis synovium suggesting increased c-Met signaling in RA synovial 
      cells. The c-Met inhibitor, SU11274, inhibited ERK1/2 and AKT phosphorylation in 
      HGF-stimulated MH7A cells. MEK and PI3K inhibitors suppressed production of 
      matrix metalloproteinase-3 (MMP-3), vascular endothelial growth factor (VEGF) and 
      prostaglandin E2 (PGE2) by MH7A cells, suggesting that c-Met-MEK-ERK and 
      c-Met-PI3K-AKT pathways are involved positively regulating MH7A cell function. 
      Although SU11274 suppressed MMP-3 and VEGF production it enhanced PGE2 production 
      by MH7A cells suggesting that negative regulation by c-Met signaling, independent 
      of the MEK-ERK and PI3K-AKT pathways, is involved in PGE2 production. Blocking 
      c-Met signaling may be therapeutically useful to inhibit angiogenesis and 
      cartilage and bone destruction by inhibiting VEGF and MMP-3 production, while 
      enhancing PGE2 production in synovial cells in RA.
FAU - Shibasaki, Seiji
AU  - Shibasaki S
AD  - General Education Center, Hyogo University of Health Sciences, 1-3-6 Minatojima, 
      Chuo-ku, Kobe, 650-8530 Japan ; Division of Rheumatology, Department of Internal 
      Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 
      663-8501 Japan.
FAU - Tsunemi, Sachi
AU  - Tsunemi S
AD  - General Education Center, Hyogo University of Health Sciences, 1-3-6 Minatojima, 
      Chuo-ku, Kobe, 650-8530 Japan.
FAU - Kitano, Sachie
AU  - Kitano S
AD  - Division of Rheumatology, Department of Internal Medicine, Hyogo College of 
      Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501 Japan.
FAU - Sekiguchi, Masahiro
AU  - Sekiguchi M
AD  - Division of Rheumatology, Department of Internal Medicine, Hyogo College of 
      Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501 Japan.
FAU - Sano, Hajime
AU  - Sano H
AD  - Division of Rheumatology, Department of Internal Medicine, Hyogo College of 
      Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501 Japan.
FAU - Iwasaki, Tsuyoshi
AU  - Iwasaki T
AD  - Division of Rheumatology, Department of Internal Medicine, Hyogo College of 
      Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501 Japan ; Division of 
      Pharmacotherapy, Department of Pharmacy, School of Pharmacy, Hyogo University of 
      Health Sciences, 1-3-6 Minatojima, Chuo-ku, Kobe, 650-8530 Japan.
LA  - eng
PT  - Journal Article
DEP - 20140923
PL  - Switzerland
TA  - Springerplus
JT  - SpringerPlus
JID - 101597967
PMC - PMC4192143
OTO - NOTNLM
OT  - Hepatocyte growth factor
OT  - Rheumatoid arthritis
OT  - Synovial cell
OT  - c-Met
EDAT- 2014/10/22 06:00
MHDA- 2014/10/22 06:01
PMCR- 2014/09/23
CRDT- 2014/10/22 06:00
PHST- 2014/06/26 00:00 [received]
PHST- 2014/09/18 00:00 [accepted]
PHST- 2014/10/22 06:00 [entrez]
PHST- 2014/10/22 06:00 [pubmed]
PHST- 2014/10/22 06:01 [medline]
PHST- 2014/09/23 00:00 [pmc-release]
AID - 1269 [pii]
AID - 10.1186/2193-1801-3-554 [doi]
PST - epublish
SO  - Springerplus. 2014 Sep 23;3:554. doi: 10.1186/2193-1801-3-554. eCollection 2014.