[CD147 stimulates the angiogenesis in rheumatoid synovium via the activation of vascular endothelial growth factor].
OBJECTIVE
To observe the correlation between vascular endothelial growth factor (VEGF) and CD147 expressed in the rheumatoid synovium and to investigate the effect of CD147 of cultured rheumatoid fibroblast-like synoviocytes (FLS) on the production of VEGF.


METHODS
The presence of CD147 and VEGF in the rheumatoid synovium derived from 15 patients with RA and 4 patients with osteoarthritis (OA) was detected by streptavidin/peroxidase (SP) immunostaining. FLS were cultured by enzymatic digestion of synovial tissues and incubated in 24-well plates. Then different concentration of LY294002, PD98059, SP600125, SB203580 and HAb18G mAb was added to each well. VEGF in the culture supernatant was measured by sandwich ELISA.


RESULTS
CD147 and VEGF in synovium from 15 patients with RA showed high expression, while CD147 and VEGF in synovium from 4 patients with OA showed low expression. Macrophages, fibroblast-like synovial cells and lymphocytes were demonstrated to express CD147 while synovial lining cells, fibroblasts surrounding microvessels and vascular smooth muscle cells were demonstrated to express VEGF. Statistic analysis indicates that VEGF production was correlated with the levels of CD147 expression. VEGFproduction was suppressed when CD147 expression was inhibited by LY294002 or HAb18G mAb.


CONCLUSIONS
CD147 can regulate the angiogenesis in rheumatoid arthritis by VEGF. The low levels of CD147 expressed by FLS cells decrease the production of VEGF via the PI3K-Akt signaling pathway. These findings further highlight the importance of CD147 in pannus formation and angiogenesis.
Wang
Cong-hua
CH
Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
Chen
Li-na
LN
Zhu
Ping
P
Fan
Chun-mei
CM
Wang
Yan-hong
YH
Jia
Jun-feng
JF
D000328:Adult; D000368:Aged; D000873:Anthracenes / Q000494:pharmacology; D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D051926:Basigin / Q000378:metabolism* / Q000502:physiology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009025:Morpholines / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D010003:Osteoarthritis / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D016133:Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D013583:Synovial Membrane / Q000166:cytology / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism* / Q000502:physiology; D055815:Young Adult
D000873:Anthracenes; D002867:Chromones; D005419:Flavonoids; D009025:Morpholines; D000081082:Phosphoinositide-3 Kinase Inhibitors; D042461:Vascular Endothelial Growth Factor A; D051926:Basigin; C432165:pyrazolanthrone; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one