Expression and localization of vascular endothelial growth factor-C in rheumatoid arthritis synovial tissue.
OBJECTIVE
Vascular endothelial growth factor-C (VEGF-C), a member of the VEGF family, induces lymphangiogenesis through VEGF receptor-3 (VEGFR-3/Flt-4). We examined the expression and localization of VEGF-C to clarify its role in synovial tissues in rheumatoid arthritis (RA).


METHODS
Reverse transcription-polymerase chain reaction (RT-PCR), Western blot analysis, immunohistochemical staining, and in situ hybridization for VEGF-C were performed on synovial tissue specimens obtained from 10 patients with RA and 4 with osteoarthritis (OA). VEGFR-3 expression was determined using Western blot analysis.


RESULTS
RT-PCR analysis showed that VEGF-C mRNA was expressed in all RA and OA synovial tissues. Based on Western blot analysis, the mature form of VEGF-C was found in RA synovial tissues, but not in OA synovial tissues, and VEGFR-3 was detected in RA and OA synovial tissues. Immunohistochemical staining showed that the VEGF-C protein was localized in many synovial lining cells, endothelial cells, and stromal cells in RA synovial tissues. In OA synovial tissues, the VEGF-C protein was localized in synovial lining cells and endothelial cells. A large number of synovial lining cells and stromal cells surrounding microvessels in RA synovial tissues expressed VEGF-C mRNA, as determined by in situ hybridization.


CONCLUSIONS
Mature VEGF-C and VEGFR-3 expression may contribute to lymphangiogenesis in RA.
Wauke
Koichi
K
Department of Joint Disease and Rheumatism and the Nippon Medical School, Tokyo, Japan.
Nagashima
Masakazu
M
Ishiwata
Toshiyuki
T
Asano
Goro
G
Yoshino
Shinichi
S
D001172:Arthritis, Rheumatoid / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002455:Cell Division / Q000502:physiology; D016228:Endothelial Growth Factors / Q000235:genetics* / Q000378:metabolism*; D004727:Endothelium / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D012333:RNA, Messenger / Q000378:metabolism*; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology; D013583:Synovial Membrane / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D042582:Vascular Endothelial Growth Factor C
D016228:Endothelial Growth Factors; D012333:RNA, Messenger; D042582:Vascular Endothelial Growth Factor C