%0 Journal Article
%T Protective Effect of Type I Collagen Antisense Oligonucleotides on Bleomycin Induced Pulmonary Fibrosis
%A Rahul K. Nath
%A Chandra Somasundaram
%A Weijun Xiong
%A Jessica Li
%A Ka BianFerid MuradBackgroundMethodsCOL1A1ResultsConclusion
%J The Open Conference Proceedings Journal
%D 2010
%I Bentham Open
%R 10.2174/2210289201001010141]
%X Background: Pulmonary fibrosis is a chronic and usually untreatable fatal lung disease. It can result from many endogenous or exogenous causes, such as infection, chronic inflammatory diseases, environmental toxins, chemical poisoning, radiation and chemotherapy. The accumulation of collagen, largely type I collagen rich extracellular matrix (ECM) is the hallmark of lung fibrosis. Current therapies for pulmonary fibrosis utilizing corticosteroids and immunosupressants have demonstrated only marginal effectiveness. Methods: In the present study, we tested the efficacy of the mouse type 1 collagen antisense oligodeoxynucleotides (AS61-ODN, a 20 mer) in bleomycin induced pulmonary fibrosis in mice. Bleomycin was instilled transtracheally by direct tracheal cut down in mice, and oligonucleotides (ODN) were injected through the tail vein. Hematoxylin and eosin (H & E) and Masson¡¯s trichrome staining were done to determine the cellular architecture of the lungs after bleomycin and oligonucleotide treatment. Type I procollagen gene COL1A1 expression was determined by Northern blot analysis. Type I collagen protein expression was determined by Western blot analysis and immunofluorescence. Results: There was much less disruption of the lung architecture as indicated by significant decrease in the Ashcroft score, when mice were injected with AS61-ODN following bleomycin instillation. AS61-ODN significantly reduced the mRNA and protein expression of type 1 collagen by 45.2 % (p < 0.015) and 35.0 % (p < 0.004) respectively 21 days after treatment in bleomycin induced fibrotic lung tissue. Immunofluorescence of bleomycin induced mouse lung tissue treated with AS61-ODN showed a specific reduction in collagen expression and fibrosis. Conclusion: Human type I collagen antisense oligodeoxynucleotides (AS60- ODN, a 20 mer), which is 99 percent homologous with mouse AS61-ODN, might be useful as a potential therapeutic agent to treat patients with pulmonary fibrosis.
%U http://www.benthamscience.com/open/toprocj/articles/V001/141TOPROCJ.htm