Mapping the future for pulmonary fibrosis.
ABSTRACT Pulmonary fibrosis is the ultimate outcome of various interstitial lung diseases, many of which have a dismal prognosis. Pulmonary fibrosis therefore represents a critical unmet medical need. Progress in research over the last 30 years has been encouraging. This work, which has been funded by governments, charitable trusts, industries and patient groups, has resulted in clinical trials testing novel drugs, giving hope to patients. In late September 2012, representatives from across academics, industry, and funding agencies met at the 17(th) International Colloquium on Airway and Lung Fibrosis Meeting to discuss state-of-the-art knowledge of pulmonary fibrosis. This manuscript summarizes the outcome of the meeting, highlighting the most relevant results and discoveries. It also attempts to provide a roadmap for future studies. It is hoped that such a roadmap may help all interested parties to generate new research, which will be vital to continued progress. We are encouraged by the commitment expressed by all participants at this meeting and the shared vision of promoting future progress through international collaboration, the pooling of valuable resources, and the involvement of new generation of physicians and scientists.
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ABSTRACT: Idiopathic pulmonary fibrosis is a disease characterized by alveolar epithelial cell injury, inflammatory cell infiltration and deposition of extracellular matrix in lung tissue. As mouse models of bleomycin-induced pulmonary fibrosis display many of the same phenotypes observed in patients with idiopathic pulmonary fibrosis, they have been used to study various aspects of the disease, including altered expression of microRNAs. In this work, microRNA expression profiling of the lungs from treated C57BL/6J mice, relative to that of untreated controls, was undertaken to determine which alterations in microRNAs could in part regulate the fibrosis phenotype induced by bleomycin delivered through mini-osmotic pumps. We identified 11 microRNAs, including miR-21 and miR-34a, to be significantly differentially expressed (P < 0.01) in lungs of bleomycin treated mice and confirmed these data with real time PCR measurements. In situ hybridization of both miR-21 and miR-34a indicated that they were expressed in alveolar macrophages. Using a previously reported gene expression profile, we identified 195 genes to be both predicted targets of the 11 microRNAs and of altered expression in bleomycin-induced lung disease of C57BL/6J mice. Pathway analysis with these 195 genes indicated that altered microRNA expression may be associated with hepatocyte growth factor signaling, cholecystokinin/gastrin-mediated signaling, and insulin-like growth factor (IGF-1) signaling, among others, in fibrotic lung disease. The relevance of the IGF-1 pathway in this model was then demonstrated by showing lung tissue of bleomycin treated C57BL/6J mice had increased expression of Igf1 and that increased numbers of Igf-1 positive cells, predominantly in macrophages, were detected in the lungs. We conclude that altered microRNA expression in macrophages is a feature which putatively influences the insulin-like growth factor signaling component of bleomycin-induced pulmonary fibrosis.Fibrogenesis & Tissue Repair 08/2013; 6(1):16. DOI:10.1186/1755-1536-6-16
- Revue des Maladies Respiratoires 12/2013; 30(10). DOI:10.1016/j.rmr.2013.10.010 · 0.49 Impact Factor
- Revue des Maladies Respiratoires 12/2013; 30(10):814-6. · 0.49 Impact Factor