Skip to main content

Advertisement

SpringerLink
Log in

Insulin-like growth factor binding protein-related protein 1 is expressed in rheumatoid synovium and regulates synovial fibroblast proliferation

  • Original Article
  • Published:
Modern Rheumatology

Abstract

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Colville-Nash PR, Scott DL. Angiogenesis and rheumatoid arthritis: pathogenic and therapeutic implications. Ann Rheum Dis. 1992;51(7):919–25.

    Article  CAS  PubMed  Google Scholar 

  2. Knedla A, Neumann E, Muller-Ladner U. Developments in the synovial biology field 2006. Arthritis Res Ther. 2007;9(2):209.

    Article  PubMed  Google Scholar 

  3. Burger AM, Leyland-Jones B, Banerjee K, Spyropoulos DD, Seth AK. Essential roles of IGFBP-3 and IGFBP-rP1 in breast cancer. Eur J Cancer. 2005;41(11):1515–27.

    Article  CAS  PubMed  Google Scholar 

  4. Hwa V, Oh Y, Rosenfeld RG. The insulin-like growth factor-binding protein (IGFBP) superfamily. Endocr Rev. 1999;20(6):761–87.

    Article  CAS  PubMed  Google Scholar 

  5. Murphy M, Pykett MJ, Harnish P, Zang KD, George DL. Identification and characterization of genes differentially expressed in meningiomas. Cell Growth Differ. 1993;4(9):715–22.

    CAS  PubMed  Google Scholar 

  6. Oh Y, Nagalla SR, Yamanaka Y, Kim HS, Wilson E, Rosenfeld RG. Synthesis and characterization of insulin-like growth factor-binding protein (IGFBP)-7. Recombinant human mac25 protein specifically binds IGF-I and -II. J Biol Chem. 1996;271(48):30322–5.

    Article  CAS  PubMed  Google Scholar 

  7. Yamauchi T, Umeda F, Masakado M, Isaji M, Mizushima S, Nawata H. Purification and molecular cloning of prostacyclin-stimulating factor from serum-free conditioned medium of human diploid fibroblast cells. Biochem J. 1994;303(Pt 2):591–8.

    CAS  PubMed  Google Scholar 

  8. Akaogi K, Okabe Y, Funahashi K, Yoshitake Y, Nishikawa K, Yasumitsu H, et al. Cell adhesion activity of a 30-kDa major secreted protein from human bladder carcinoma cells. Biochem Biophys Res Commun. 1994;198(3):1046–53.

    Article  CAS  PubMed  Google Scholar 

  9. Akaogi K, Okabe Y, Sato J, Nagashima Y, Yasumitsu H, Sugahara K, et al. Specific accumulation of tumor-derived adhesion factor in tumor blood vessels and in capillary tube-like structures of cultured vascular endothelial cells. Proc Natl Acad Sci USA. 1996;93(16):8384–9.

    Article  CAS  PubMed  Google Scholar 

  10. Burger AM, Zhang X, Li H, Ostrowski JL, Beatty B, Venanzoni M, et al. Down-regulation of T1A12/mac25, a novel insulin-like growth factor binding protein related gene, is associated with disease progression in breast carcinomas. Oncogene. 1998;16(19):2459–67.

    Article  CAS  PubMed  Google Scholar 

  11. Burger AM, Zhang X, Seth A. Detection of novel genes that are up-regulated (Di12) or down-regulated (T1A12) with disease progression in breast cancer. Eur J Cancer Prev. 1998;7(Suppl 1):S29–35.

    Article  PubMed  Google Scholar 

  12. Sato J, Hasegawa S, Akaogi K, Yasumitsu H, Yamada S, Sugahara K, et al. Identification of cell-binding site of angiomodulin (AGM/TAF/Mac25) that interacts with heparin sulfates on cell surface. J Cell Biochem. 1999;75(2):187–95.

    Article  CAS  PubMed  Google Scholar 

  13. Yamanaka Y, Wilson EM, Rosenfeld RG, Oh Y. Inhibition of insulin receptor activation by insulin-like growth factor binding proteins. J Biol Chem. 1997;272(49):30729–34.

    Article  CAS  PubMed  Google Scholar 

  14. Kato MV, Sato H, Tsukada T, Ikawa Y, Aizawa S, Nagayoshi M. A follistatin-like gene, mac25, may act as a growth suppressor of osteosarcoma cells. Oncogene. 1996;12(6):1361–4.

    CAS  PubMed  Google Scholar 

  15. Swisshelm K, Ryan K, Tsuchiya K, Sager R. Enhanced expression of an insulin growth factor-like binding protein (mac25) in senescent human mammary epithelial cells and induced expression with retinoic acid. Proc Natl Acad Sci USA. 1995;92(10):4472–6.

    Article  CAS  PubMed  Google Scholar 

  16. Sprenger CC, Vail ME, Evans K, Simurdak J, Plymate SR. Over-expression of insulin-like growth factor binding protein-related protein-1 (IGFBP-rP1/mac25) in the M12 prostate cancer cell line alters tumor growth by a delay in G1 and cyclin A associated apoptosis. Oncogene. 2002;21(1):140–7.

    Article  CAS  PubMed  Google Scholar 

  17. Wilson HM, Birnbaum RS, Poot M, Quinn LS, Swisshelm K. Insulin-like growth factor binding protein-related protein 1 inhibits proliferation of MCF-7 breast cancer cells via a senescence-like mechanism. Cell Growth Differ. 2002;13(5):205–13.

    CAS  PubMed  Google Scholar 

  18. Pereira RC, Blanquaert F, Canalis E. Cortisol enhances the expression of mac25/insulin-like growth factor-binding protein-related protein-1 in cultured osteoblasts. Endocrinology. 1999;140(1):228–32.

    Article  CAS  PubMed  Google Scholar 

  19. Akaogi K, Sato J, Okabe Y, Sakamoto Y, Yasumitsu H, Miyazaki K. Synergistic growth stimulation of mouse fibroblasts by tumor-derived adhesion factor with insulin-like growth factors and insulin. Cell Growth Differ. 1996;7(12):1671–7.

    CAS  PubMed  Google Scholar 

  20. Sakurai N, Kuroiwa T, Ikeuchi H, Hiramatsu N, Maeshima A, Kaneko Y, et al. Expression of IL-19 and its receptors in RA: potential role for synovial hyperplasia formation. Rheumatology (Oxford). 2008;47(6):815–20.

    Article  CAS  Google Scholar 

  21. Ikeuchi H, Kuroiwa T, Hiramatsu N, Kaneko Y, Hiromura K, Ueki K, et al. Expression of interleukin-22 in rheumatoid arthritis: potential role as a proinflammatory cytokine. Arthritis Rheum. 2005;52(4):1037–46.

    Article  CAS  PubMed  Google Scholar 

  22. Morel J, Audo R, Hahne M, Combe B. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces rheumatoid arthritis synovial fibroblast proliferation through mitogen-activated protein kinases and phosphatidylinositol 3-kinase/Akt. J Biol Chem. 2005;280(16):15709–18.

    Article  CAS  PubMed  Google Scholar 

  23. Suzuki M, Tetsuka T, Yoshida S, Watanabe N, Kobayashi M, Matsui N, et al. The role of p38 mitogen-activated protein kinase in IL-6 and IL-8 production from the TNF-alpha- or IL-1beta-stimulated rheumatoid synovial fibroblasts. FEBS Lett. 2000;465(1):23–7.

    Article  CAS  PubMed  Google Scholar 

  24. Granet C, Maslinski W, Miossec P. Increased AP-1 and NF-kappaB activation and recruitment with the combination of the proinflammatory cytokines IL-1beta, tumor necrosis factor alpha and IL-17 in rheumatoid synoviocytes. Arthritis Res Ther. 2004;6(3):R190–8.

    Article  CAS  PubMed  Google Scholar 

  25. Jiang W, Xiang C, Cazacu S, Brodie C, Mikkelsen T. Insulin-like growth factor binding protein 7 mediates glioma cell growth and migration. Neoplasia. 2008;10(12):1335–42.

    CAS  PubMed  Google Scholar 

  26. Usui T, Murai T, Tanaka T, Yamaguchi K, Nagakubo D, Lee CM, et al. Characterization of mac25/angiomodulin expression by high endothelial venule cells in lymphoid tissues and its identification as an inducible marker for activated endothelial cells. Int Immunol. 2002;14(11):1273–82.

    Article  CAS  PubMed  Google Scholar 

  27. Pen A, Moreno MJ, Durocher Y, Deb-Rinker P, Stanimirovic DB. Glioblastoma-secreted factors induce IGFBP7 and angiogenesis by modulating Smad-2-dependent TGF-beta signaling. Oncogene. 2008;27(54):6834–44.

    Article  CAS  PubMed  Google Scholar 

  28. Nagakubo D, Murai T, Tanaka T, Usui T, Matsumoto M, Sekiguchi K, et al. A high endothelial venule secretory protein, mac25/angiomodulin, interacts with multiple high endothelial venule-associated molecules including chemokines. J Immunol. 2003;171(2):553–61.

    CAS  PubMed  Google Scholar 

  29. Fernihough JK, Billingham ME, Cwyfan-Hughes S, Holly JM. Local disruption of the insulin-like growth factor system in the arthritic joint. Arthritis Rheum. 1996;39(9):1556–65.

    Article  CAS  PubMed  Google Scholar 

  30. Neidel J. Changes in systemic levels of insulin-like growth factors and their binding proteins in patients with rheumatoid arthritis. Clin Exp Rheumatol. 2001;19(1):81–4.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We thank Ms. Rumiko Koitabashi for her excellent technical assistance. This work was supported in part by a grant from the Japanese Ministry of Education, Culture, Sports, Science and Technology.

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Department of Medicine and Clinical Science, Gunma University Graduate School of Medicine, 3-39-15 Showa, Maebashi, Gunma, 371-8511, Japan

    Noriyuki Sakurai, Takashi Kuroiwa, Ken Kayakabe, Takayuki Matsumoto, Akito Maeshima, Keiju Hiromura & Yoshihisa Nojima

Authors
  1. Noriyuki Sakurai
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Takashi Kuroiwa
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ken Kayakabe
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Takayuki Matsumoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Akito Maeshima
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Keiju Hiromura
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yoshihisa Nojima
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Noriyuki Sakurai.

About this article

Cite this article

Sakurai, N., Kuroiwa, T., Kayakabe, K. et al. Insulin-like growth factor binding protein-related protein 1 is expressed in rheumatoid synovium and regulates synovial fibroblast proliferation. Mod Rheumatol 21, 63–72 (2011). https://doi.org/10.1007/s10165-010-0353-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10165-010-0353-z

Keywords

Search

Navigation