Skip to main content

Advertisement

Log in

TSP-1 in lung fibrosis

  • Commentary
  • Published:
Journal of Cell Communication and Signaling Aims and scope

Abstract

Lung fibrosis is often treated with corticosteroids to reduce the inflammatory response, however, no effective treatment options exist for the underlying disease. An important player in the fibrotic cascade is the cytokine, transforming growth factor beta (TGFβ). TGFβ is converted from an inactive procytokine complex to active TGFβ by enzymes such as thrombospondin-1 (TSP-1). It is therefore presumed that TSP-1 deficient mice would fare better to bleomycin-induced pulmonary fibrosis because TGFβ would not be efficiently converted to the active form. Interestingly, a recent article by Ezzie and colleagues shows that TSP-1 deficiency does not protect mice from systemic bleomycin challenge. Indeed, they find the opposite, as TSP-1-null mice appear to exhibit greater lung fibrosis than wild type mice, although similar TGFβ signaling was observed in the lungs of both mouse strains.

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

Access this article

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

Instant access to the full article PDF.

References

  • Ali NA, Gaughan AA, Orosz CG, Baran CP, McMaken S, Wang Y, Eubank TD, Hunter M, Lichtenberger FJ, Flavahan NA, Lawler J, Marsh CB (2008) Latency associated peptide has in vitro and in vivo immune effects independent of TGF-beta1. PLoS ONE 3:e1914

    Article  PubMed  Google Scholar 

  • Attisano L, Wrana JL (2002) Signal transduction by the TGF-beta superfamily. Science 296:1646–1647

    Article  CAS  PubMed  Google Scholar 

  • Chen Y, Wang X, Weng D, Tian L, Lv L, Tao S, Chen J (2009) A TSP-1 synthetic peptide inhibits bleomycin-induced lung fibrosis in mice. Exp Toxicol Pathol 61:59–65

    Article  CAS  PubMed  Google Scholar 

  • Daniel C, Takabatake Y, Mizui M, Isaka Y, Kawashi H, Rupprecht H, Imai E, Hugo C (2003) Antisense oligonucleotides against thrombospondin-1 inhibit activation of tgf-beta in fibrotic renal disease in the rat in vivo. Am J Pathol 163:1185–1192

    CAS  PubMed  Google Scholar 

  • Daniel C, Wiede J, Krutzsch HC, Ribeiro SM, Roberts DD, Murphy-Ullrich JE, Hugo C (2004) Thrombospondin-1 is a major activator of TGF-beta in fibrotic renal disease in the rat in vivo. Kidney Int 65:459–468

    Article  CAS  PubMed  Google Scholar 

  • Ezzie ME, Piper MG, Montague C, Newland CA, Opalek JM, Baran C, Ali N, Brigstock D, Lawler J, Marsh CB (2010) Thrombospondin-1 deficient mice are not protected from bleomycin-induced pulmonary fibrosis. Am J Respir Cell Mol Biol

  • Massague J (1998) TGF-beta signal transduction. Annu Rev Biochem 67:753–791

    Article  CAS  PubMed  Google Scholar 

  • Munger JS, Huang X, Kawakatsu H, Griffiths MJ, Dalton SL, Wu J, Pittet JF, Kaminski N, Garat C, Matthay MA, Rifkin DB, Sheppard D (1999) The integrin alpha v beta 6 binds and activates latent TGF beta 1: a mechanism for regulating pulmonary inflammation and fibrosis. Cell 96:319–328

    Article  CAS  PubMed  Google Scholar 

  • Papadaki C, Mavroudis D, Trypaki M, Koutsopoulos A, Stathopoulos E, Hatzidaki D, Tsakalaki E, Georgoulias V, Souglakos J (2009) Tumoral expression of TXR1 and TSP1 predicts overall survival of patients with lung adenocarcinoma treated with first-line docetaxel-gemcitabine regimen. Clin Cancer Res 15:3827–3833

    Article  CAS  PubMed  Google Scholar 

  • Ribeiro SM, Poczatek M, Schultz-Cherry S, Villain M, Murphy-Ullrich JE (1999) The activation sequence of thrombospondin-1 interacts with the latency-associated peptide to regulate activation of latent transforming growth factor-beta. J Biol Chem 274:13586–13593

    Article  CAS  PubMed  Google Scholar 

  • Schultz-Cherry S, Murphy-Ullrich JE (1993) Thrombospondin causes activation of latent transforming growth factor-beta secreted by endothelial cells by a novel mechanism. J Cell Biol 122:923–932

    Article  CAS  PubMed  Google Scholar 

  • Yamaguchi M, Sugio K, Ondo K, Yano T, Sugimachi K (2002) Reduced expression of thrombospondin-1 correlates with a poor prognosis in patients with non-small cell lung cancer. Lung Cancer 36:143–150

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Gianni M. Di Guglielmo.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Di Guglielmo, G.M. TSP-1 in lung fibrosis. J. Cell Commun. Signal. 4, 185–186 (2010). https://doi.org/10.1007/s12079-010-0097-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12079-010-0097-8

Keywords

Navigation