Functional analysis of discoidin domain receptor 2 in synovial fibroblasts in rheumatoid arthritis.
In order to know whether any protein tyrosine kinase (PTK) is involved in the over-proliferation and erosiveness of synovial fibroblasts (SF) of rheumatoid arthritis (RA) patients, RT-PCR and RNA dot blotting were done to analyse PTKs profile in RA SF. Platelet-derived growth factor receptor A (PDGFRA), insulin-like growth factor 1 receptor (IGF-1R), Janus kinase 1 (JAK1), TYK2, discoidin domain receptor 2 (DDR2), and Lyn were expressed in SF, and the expression of PDGFRA, IGF-1R, and DDR2 in SF of RA were higher than that of osteoarthritis (OA, as control). Immunoblotting and gelatinase zymography showed that DDR2 in RA SF, which still secreted active matrix metalloproteinase 1 (MMP-1) in vitro, were in active form. Stimulation of collagen II could make NIH-3T3 cells (as control) produce MMP-1, which could be inhibited by soluble extracellular part of DDR2. These results indicated that the over-expression of MMP-1 in RA SF might be related to the activation of DDR2, and collagen II, act as DDR2 ligand, might be one of the stimulators of the over-expression of MMP-1 of RA SF.
Wang
Jicun
J
Department of Biochemistry and Molecular Biology, The Fourth Military Medical University, Xi'an, People's Republic of China.
Lü
Houshan
H
Liu
Xinping
X
Deng
Yanchun
Y
Sun
Tiezheng
T
Li
Fuyang
F
Ji
Shaoping
S
Nie
Xiaoyan
X
Yao
Libo
L
D016475:3T3 Cells; D000818:Animals; D001172:Arthritis, Rheumatoid / Q000201:enzymology / Q000378:metabolism*; D024043:Collagen Type II / Q000378:metabolism; D000070818:Discoidin Domain Receptors; D005347:Fibroblasts / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D051379:Mice; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D011975:Receptors, Mitogen / Q000378:metabolism*; D013583:Synovial Membrane / Q000201:enzymology / Q000473:pathology; D015854:Up-Regulation
D024043:Collagen Type II; D011975:Receptors, Mitogen; D000070818:Discoidin Domain Receptors; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases; D020781:Matrix Metalloproteinase 1