Skip to main content

Advertisement

SpringerLink
Log in

Tissue repair driven by two different mechanisms of growth factor plasmids VEGF and NGF in mice auricular cartilage: regeneration mediated by administering growth factor plasmids

  • Otology
  • Published:
European Archives of Oto-Rhino-Laryngology Aims and scope Submit manuscript

Abstract

The focus of this study was to compare the role of nerve growth factor (NGF) and vascular endothelial growth factor (VEGF) in the regeneration of experimental skin and cartilage trauma. The role of VEGF in this process is known since decade; the NGF participation on this process has been first discussed within the spinal cord injury repair. We hypothesized that both VEGF and NGF induce angiogenesis and take part on the repair process. The angiogenesis response and the cartilage regeneration after phVEGF165 plasmid and rat pcNGF plasmid administration were investigated using BALB/c mice. PhVEGF165 and pcNFG were injected into the right mice ear and plain vector injection into the left ear the day before trauma. The next day, all mice were ear-punched, resulting in 2-mm diameter puncture through the center of both pinnae. In BALB/c mouse strain, a significantly faster cartilage repair was observed after phVEGF165 and pcNGF injection into punched ear area in comparison to the control group. It has been shown that the healing process is after VEGF and NGF injection driven differentially. In case of VEGF is the cartilage wound repaired by induction of new chondrocytes differentiation. In the case of NGF, the regeneration is supported by immature leukocytes attracted into the punched area. The leukocytes induct angiogenesis so far indirectly by inflammation. The NGF-induced inflammation environment may be a part of mosaic creating the complete picture of regeneration.

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

Similar content being viewed by others

References

  1. Ansel JC, Brown JR, Payan DG, Brown MA (1993) Substance P selectively activates TNF-alpha gene expression in murine mast cells. J Immunol 150:4478

    PubMed  CAS  Google Scholar 

  2. Cantarella G, Lempereur L, Presta M, Ribatti D, Lombardo G, Lazarovici P, Zappala G, Pafumi C, Bernardini R (2002) Nerve growth factor-endothelial cell interaction leads to angiogenesis in vitro and in vivo. FASEB J 16:1307

    PubMed  CAS  Google Scholar 

  3. Carlevaro MF, Cermelli S, Cancedda R, Descalzi Cancedda F (2000) Vascular endothelial growth factor (VEGF) in cartilage neovascularization and chondrocyte differentiation: auto-paracrine role during endochondral bone formation. J Cell Sci 113(Pt 1):59

    PubMed  CAS  Google Scholar 

  4. Cordeiro PG, Seckel BR, Lipton SA, D’Amore PA, Wagner J, Madison R (1989) Acidic fibroblast growth factor enhances peripheral nerve regeneration in vivo. Plast Reconstr Surg 83:1013

    Article  PubMed  CAS  Google Scholar 

  5. Dvorak HF, Nagy JA, Feng D, Brown LF, Dvorak AM (1999) Vascular permeability factor/vascular endothelial growth factor and the significance of microvascular hyperpermeability in angiogenesis. Curr Top Microbiol Immunol 237:97

    Article  PubMed  CAS  Google Scholar 

  6. Emanueli C, Salis MB, Pinna A, Graiani G, Manni L, Madeddu P (2002) Nerve growth factor promotes angiogenesis in ishcemic hindlimbs. Circulation 106:2257

    Article  PubMed  CAS  Google Scholar 

  7. Eppley BL, Doucet M, Connolly DT, Feder J (1988) Enhancement of angiogenesis by bFGF in mandibular bone graft healing in the rabbit. J Oral Maxillofac Surg 46:391

    Article  PubMed  CAS  Google Scholar 

  8. Fukino K, Sata M, Seko Y, Hirata Y, Nagai R (2003) Genetic background influences therapeutic effectiveness of VEGF. Biochem Biophys Res Commun 310:143

    Article  PubMed  CAS  Google Scholar 

  9. Gerber HP, Vu TH, Ryan AM, Kowalski J, Werb Z, Ferrara N (1999) VEGF couples hypertrophic cartilage remodeling, ossification and angiogenesis during endochondral bone formation. Nat Med 5:623

    Article  PubMed  CAS  Google Scholar 

  10. Graiani G, Emanueli C, Desortes E, Van Linhout S, Pinna A, Figureoa CD, Manni L, MAdeddu P (2004) Nerve growth factor promoted reparative angiogenesis and inhibits endothelial apoptosis in cutaneous wounds of Type 1 diabetic mice. Diabetologia 47:1047

    Article  PubMed  CAS  Google Scholar 

  11. Iannone F, De Bari C, Dell’Accio F, Covelli M, Patella V, LoBianco G, Lapadula G (2002) Increased expression of nerve growth factor (NGF) and high affinity NGF receptor (p140TrkA) in human osteoarthritic chondrocytes. Rheumatology 41:1413

    Article  PubMed  CAS  Google Scholar 

  12. Isner JM, Pieczek A, Schainfeld R, Blair R, Haley L, Asahara T, Rosenfield K, Razvi S, Walsh K, Symes JF (1996) Clinical evidence of angiogenesis after arterial gene transfer of phVEGF165 in patient with ischaemic limb. Lancet 348:370

    Article  PubMed  CAS  Google Scholar 

  13. Isner JM, Rosenfield K (1993) Redefining the treatment of peripheral artery disease. Role of percutaneous revascularization. Circulation 88:1534

    PubMed  CAS  Google Scholar 

  14. Khouri RK, Hong SP, Deune EG, Tarpley JE, Song SZ, Serdar CM, Pierce GF (1994) De novo generation of permanent neovascularized soft tissue appendages by platelet-derived growth factor. J Clin Invest 94:1757

    Article  PubMed  CAS  Google Scholar 

  15. Levi-Montalcini R (1987) The nerve growth factor 35 years later. Science 237:1154

    Article  PubMed  CAS  Google Scholar 

  16. Manni L, Antonelli A, Costa N, Aloe L (2005) Stress alters vascular-endothelial growth factor expression in rat arteries: role of nerve growth factor. Basic Res Cardiol 2005:121

    Article  Google Scholar 

  17. Matsuda H, Koyama H, Sato H (1998) Role of nerve growth factor in cutaneous wound healing: accelerating effects in normal and healing-impaired diabetic mice. J Exp Med 187:297

    Article  PubMed  CAS  Google Scholar 

  18. Nomoto H, Takaiwa M, Mouri A, Furukawa S (2007) Pro-region of neurotrophins determines the processing efficiency. Biochem Biophys Res Commun 18;356(4):919–924

    Article  Google Scholar 

  19. Olech VM, Keshavjee SH, Chamberlain DW, Slutsky AS, Patterson GA (1991) Role of basic fibroblast growth factor in revascularization of rabbit tracheal autografts. Ann Thorac Surg 52:258

    Article  PubMed  CAS  Google Scholar 

  20. Payan DG, McGillis JP, Renold FK, Mitsuhashi M, Goetzl EJ (1987) Neuropeptide modulation of leukocyte function. Ann N Y Acad Sci 496:182

    Article  PubMed  CAS  Google Scholar 

  21. Petersen W, Pufe T, Starke C, Fuchs T, Kopf S, Raschke M, Becker R, Tillmann B (2005) Locally applied angiogenic factors—a new therapeutic tool for meniscal repair. Ann Anat 187:509

    Article  PubMed  CAS  Google Scholar 

  22. Raychaudhuri SK, Raychaudhuri PS, Weltman H, Farber EM (2001) Effect of nerve growth factor on endothelial cell biology: proliferation and adherence molecule expression on human dermal microvascular endothelial cells. Arch Dermatol Res 293:291

    Article  PubMed  CAS  Google Scholar 

  23. Spyridopoulos I, Brogi E, Kearney M, Sullivan AB, Cetrulo C, Isner JM, Losordo DW (1997) Vascular endothelial growth factor inhibits endothelial cell apoptosis induced by tumor necrosis factor-alpha: balance between growth and death signals. J Mol Cell Cardiol 29:1321

    Article  PubMed  CAS  Google Scholar 

  24. Street J, Bao M, deGuzman L, Bunting S, Peale FV Jr, Ferrara N, Steinmetz H, Hoeffel J, Cleland JL, Daugherty A, van Bruggen N, Redmond HP, Carano RA, Filvaroff EH (2002) Vascular endothelial growth factor stimulates bone repair by promoting angiogenesis and bone turnover. Proc Natl Acad Sci USA 99:9656

    Article  PubMed  CAS  Google Scholar 

  25. Takeshita S, Isshiki T, Ochiai M, Eto K, Mori H, Tanaka E, Umetani K, Sato T (1998) Endothelium-dependent relaxation of collateral microvessels after intramuscular gene transfer of vascular endothelial growth factor in a rat model of hindlimb ischemia. Circulation 98:1261

    PubMed  CAS  Google Scholar 

  26. Taylor PC (2002) VEGF and imaging of vessels in rheumatoid arthritis. Arthritis Res 4(Suppl 3):S99

    Article  PubMed  Google Scholar 

  27. Tsurumi Y, Takeshita S, Chen D, Kearney M, Rossow ST, Passeri J, Horowitz JR, Symes JF, Isner JM (1996) Direct intramuscular gene transfer of naked DNA encoding vascular endothelial growth factor augments collateral development and tissue perfusion. Circulation 94:3281

    PubMed  CAS  Google Scholar 

  28. Yanagisawa-Miwa A, Uchida Y, Nakamura F, Tomaru T, Kido H, Kamijo T, Sugimoto T, Kaji K, Utsuyama M, Kurashima C et al (1992) Salvage of infarcted myocardium by angiogenic action of basic fibroblast growth factor. Science 257:1401

    Article  PubMed  CAS  Google Scholar 

  29. Yancopoulos GD, Davis S, Gale NW, Rudge JS, Wiegand SJ, Holash J (2000) Vascular-specific growth factors and blood vessel formation. Nature 407:242

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The study was supported by the research project MSM No. 002 162 0816 and by research project MŠMT ME831 at the Third Faculty of Medicine Charles University Prague and by the research project of the MSM No. 002 162 0807.

Author information

Authors and Affiliations

  1. Department of Tumor Biology, Third Faculty of Medicine, Charles University Prague, Ruska 87, 100 34, Prague 10, Czech Republic

    Katarina Kolostova, Oliver Taltynov, Daniela Pinterova & Vladimir Bobek

  2. CGB Laboratory Inc., Ostrava, Czech Republic

    Martin Cegan & Lenka Ceganova

  3. Department of Surgery, Third Faculty of Medicine, University Hospital Kralovske Vinohrady, Prague, Czech Republic

    Vladimir Bobek

  4. Institute of Histology and Embryology, First Faculty of Medicine, Charles University Prague, Prague, Czech Republic

    Marie Jirkovska

Authors
  1. Katarina Kolostova
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Oliver Taltynov
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Daniela Pinterova
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Martin Cegan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Lenka Ceganova
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Marie Jirkovska
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Vladimir Bobek
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Vladimir Bobek.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kolostova, K., Taltynov, O., Pinterova, D. et al. Tissue repair driven by two different mechanisms of growth factor plasmids VEGF and NGF in mice auricular cartilage: regeneration mediated by administering growth factor plasmids. Eur Arch Otorhinolaryngol 269, 1763–1770 (2012). https://doi.org/10.1007/s00405-011-1821-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00405-011-1821-6

Keywords

Search

Navigation