Poster Presentations: Wednesday, November 3, 2010 |

Suppression of Thrombospondin-1 by RNA Interference Attenuates FITC-Induced Murine Pulmonary Fibrosis FREE TO VIEW

Hiroaki Oka, MD; Hiroshi Ishii, MD; Atsuko Iwata, MD; Kosaku Komiya, MD; Jun-ichi Kadota, MD
Author and Funding Information

Internal Medicine II, Oita University Faculty of Medicine, Yufu, Japan

Chest. 2010;138(4_MeetingAbstracts):526A. doi:10.1378/chest.9989
Text Size: A A A
Published online


PURPOSE: Emerging evidence supports a major role for a thrombospondin-1 (TSP-1) and transforming growth factor-β (TGF-β) axis in fibrotic disease. TSP-1 can activate latent TGF-β, an important profibrotic cytokine involved in various fibrotic diseases. The aim of this study is to evaluate a role of TSP-1 in pulmonary fibrosis.

METHODS: Serum and bronchoalveolar lavage fluid levels of TSP-1 were measured by a competitive enzyme immunoassay in patients with idiopathic interstitial pneumonias (IIPs). Expression and localization of TSP-1 in their lung specimens was analyzed by immunohistochemical staining. The inhibitory effect of suppression of TSP-1 was evaluated following the single intratracheal administration of TSP-1-siRNA in a mouse model of FITC-induced pulmonary fibrosis.

RESULTS: The serum TSP-1 levels were significantly higher in patients with IIPs than in those with the controls. These levels correlated inversely with the %VC. TSP-1 was overexpressed predominantly in the hyperplastic type 2 pneumocytes and alveolar macrophages in the lung. The administration of TSP-1-siRNA into FITC-injured mice limited the alveolitis and the accumulation of collagen in the lungs.

CONCLUSION: Our results suggest an association between the serum TSP-1 levels and the presence of interstitial fibrosis. The direct suppression of TSP-1 in the lung by the intratracheal administration of TSP-1-siRNA attenuated the development and progression of pulmonary fibrosis.

CLINICAL IMPLICATIONS: TSP-1 might have a potential as a molecular target for therapeutic intervention in the treatment of fibrotic lung diseases. Further studies are required.

DISCLOSURE: Hiroaki Oka, No Financial Disclosure Information; No Product/Research Disclosure Information

12:45 PM - 2:00 PM




Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging & repositioning the boxes below.

CHEST Journal Articles
  • CHEST Journal
    Print ISSN: 0012-3692
    Online ISSN: 1931-3543