title: Expression and localization of vascular endothelial growth factor-C in rheumatoid arthritis synovial tissue.
abstract: 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.
authors.affiliation: Department of Joint Disease and Rheumatism and the Nippon Medical School, Tokyo, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Wauke
authors.forename: Masakazu
authors.initials: M
authors.lastname: Nagashima
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Ishiwata
authors.forename: Goro
authors.initials: G
authors.lastname: Asano
authors.forename: Shinichi
authors.initials: S
authors.lastname: Yoshino
mesh_terms: 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
chemical_list: D016228:Endothelial Growth Factors; D012333:RNA, Messenger; D042582:Vascular Endothelial Growth Factor C