Insulin-like growth factor binding protein-related protein 1 is expressed in rheumatoid synovium and regulates synovial fibroblast proliferation.
Insulin-like growth factor binding protein-related protein 1 (IGFBP-rP1) is a secretory protein that shares a structural similarity with IGFBP. Studies have shown that IGFBP-rP1 synergistically increases fibroblast growth with insulin and stimulates angiogenesis in tumor tissues. In this report, we examined the expression and function of IGFBP-rP1 in rheumatoid arthritis (RA). IGFBP-rP1 expression in synovial tissues was examined by reverse transcription-polymerase chain reaction (RT-PCR), real-time PCR, and immunohistochemical analysis. In vitro, IGFBP-rP1 expression was examined in synovial fibroblasts established from rheumatoid synovium (RASFs) by RT-PCR, Western blot, and immunostaining. The effect of IGFBP-rP1 small interfering RNA (siRNA) on RASF proliferation was assessed by alamarBlue assay. IGFBP-rP1 mRNA was detected by RT-PCR in all synovial tissues from RA and OA patients. In immunohistochemical analysis, IGFBP-rP1 was mainly expressed in synovial cells in the lining layers and endothelial cells in the sublining layers of RA synovium. In vitro, constitutive expression of IGFBP-rP1 in RASFs was detected by RT-PCR, Western blot, and immunostaining. Treatment with IGFBP-rP1 siRNA induced a 26% decrease in RASF growth compared to control siRNA. A similar extent of growth-suppressive effect by IGFBP-rP1 siRNA was also observed when RASF proliferation was induced by TNF-α. Collectively, these data suggest that IGFBP-rP1 may regulate synovial fibroblast proliferation in RA.
Sakurai
Noriyuki
N
Department of Medicine and Clinical Science, Gunma University Graduate School of Medicine, 3-39-15 Showa, Maebashi, Gunma, 371-8511, Japan. nysakura@med.gunma-u.ac.jp
Kuroiwa
Takashi
T
Kayakabe
Ken
K
Matsumoto
Takayuki
T
Maeshima
Akito
A
Hiromura
Keiju
K
Nojima
Yoshihisa
Y
D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000378:metabolism* / Q000601:surgery; D049109:Cell Proliferation / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D015870:Gene Expression; D020868:Gene Silencing; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000378:metabolism* / Q000601:surgery; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism / Q000494:pharmacology; D011994:Recombinant Proteins; D013583:Synovial Membrane / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology
D018969:Insulin-Like Growth Factor Binding Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; C102529:insulin-like growth factor binding protein-related protein 1