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.

Conclusion: Mature VEGF-C and VEGFR-3 expression may contribute to lymphangiogenesis in RA.