A Micro RNA Processing Defect in Rapidly Progressing Idiopathic Pulmonary Fibrosis

Oak, Sameer R.; Murray, Lynne A.; Herath, Athula; Sleeman, Matthew A.; Anderson, Ian; Joshi, Amrita; Coelho, Ana Lúcia; Flaherty, Kevin R.; Toews, Galen B.; Knight, Darryl A.; Martínez, Fernando J.; Hogaboam, Cory M.

doi:10.1371/journal.pone.0021253

Cited by 126 publications

(97 citation statements)

References 63 publications

(91 reference statements)

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“…Classical gene expression profiling studies have progressed in IPF from characterizations of small numbers of human or mouse lung samples to analyses of large cohorts that have led to identification of multiple relevant genes (92)(93)(94)(95). Progress has been made in novel profiling of IPF as well: mechanistically relevant changes in microRNA expression profiles in IPF lung have been described (96)(97)(98), and studies aimed at determining the lung methylome are ongoing (99,100). Investigators can now access the Lung Genomics Research Consortium website (http://www.lung-genomics.org/lgrc) and download mRNA, microRNA, methylation, and SNP profiles of carefully phenotyped IPF lungs.…”

Section: Profiling Of Pulmonary Fibrosis Using Novel Techniquesmentioning

confidence: 99%

Future Directions in Idiopathic Pulmonary Fibrosis Research. An NHLBI Workshop Report

Blackwell

Tager

Borok

et al. 2014

Am J Respir Crit Care Med

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213

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The median survival of patients with idiopathic pulmonary fibrosis (IPF) continues to be approximately 3 years from the time of diagnosis, underscoring the lack of effective medical therapies for this disease. In the United States alone, approximately 40,000 patients die of this disease annually. In November 2012, the NHLBI held a workshop aimed at coordinating research efforts and accelerating the development of IPF therapies. Basic, translational, and clinical researchers gathered with representatives from the NHLBI, patient advocacy groups, pharmaceutical companies, and the U.S. Food and Drug Administration to review the current state of IPF research and identify priority areas, opportunities for collaborations, and directions for future research. The workshop was organized into groups that were tasked with assessing and making recommendations to promote progress in one of the following six critical areas of research: (1) biology of alveolar epithelial injury and aberrant repair; (2) role of extracellular matrix; (3) preclinical modeling; (4) role of inflammation and immunity; (5) genetic, epigenetic, and environmental determinants; (6) translation of discoveries into diagnostics and therapeutics. The workshop recommendations provide a basis for directing future research and strategic planning by scientific, professional, and patient communities and the NHLBI.

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Section: Profiling Of Pulmonary Fibrosis Using Novel Techniquesmentioning

confidence: 99%

Future Directions in Idiopathic Pulmonary Fibrosis Research. An NHLBI Workshop Report

Blackwell

Tager

Borok

et al. 2014

Am J Respir Crit Care Med

Self Cite

213

192

View full text Add to dashboard Cite

show abstract

“…More recently, the abnormal expression of mRNAs has also been associated with the pathogenesis of both cancer and IPF. mRNAs are short nonprotein-coding RNA strands that may regulate the expression of related target genes involved in the control of different processes linked to carcinogenesis, such as tumour growth, invasion and metastasis [24][25][26]. Recently, it has been shown that ,10% of mRNAs are abnormally expressed in IPF, some of them, such as let-7, miR-29, miR-30 and miR-200, are significantly downregulated, while miR-155 and miR-21 are instead upregulated.…”

Section: Epigenetic and Genetic Abnormalities In Ipf And Cancermentioning

confidence: 99%

Common pathways in idiopathic pulmonary fibrosis and cancer

Vancheri¹

2013

Eur Respir Rev

149

105

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Idiopathic pulmonary fibrosis (IPF) is marked by a very disappointing survival rate and still represents a clinical dilemma. According to the current pathogenic hypothesis, chronic damage of the alveolar epithelium is followed by abnormal tissue repair and impairment of the alveolar structure. This process is driven by pathogenic events very similar to cancer, including epigenetic and genetic changes, altered response to regulatory signals, abnormal expression of microRNAs and activation of specific signalling pathways. IPF also resembles cancer with regard to its poor response to medical treatment and prognosis, which is very often worse than many cancers. We have hypothesised that IPF might be assimilated to a neoproliferative disorder of the lung. Viewing IPF as a cancer-like disease may satisfy the need for a better understanding of the pathogenesis of IPF by exploiting the large amount of knowledge that cancer biology evokes. The recognition of common pathogenic pathways between the two diseases may stimulate new clinical trials with cancer drugs, different drug combinations and different lines of drugs, as already experimented in oncology. Moreover, the concept of IPF as a cancer-like disorder may improve the attention given to this dreadful disease on a public, political and healthcare level. @ERSpublications Considering idiopathic pulmonary fibrosis as a cancer-like disorder may improve its treatment and investigation.

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“…The IPF patient population was further subdivided into slow and rapid progressors as previously described [26]. We noticed a decrease in the epithelial markers keratin 18 and keratin 19 in both slow and rapid progressors ( Figure 5(a)).…”

Section: Alterations In Epithelial Mesenchymal and Apoptotic Markersmentioning

confidence: 62%

An Assessment of Epithelial and Mesenchymal Phenotypes in Experimental and Clinical Pulmonary Fibrosis

et al. 2012

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Epithelial injury has been implicated as a driving factor for the pathogenesis of idiopathic pulmonary fibrosis (IPF). In this study we investigated changes in epithelial and mesenchymal markers in experimental models of fibrosis and associated this with IPF. TGFβ 1 induced an epithelial to mesenchymal transition (EMT) phenotype in A549 cells and normal human bronchial epithelial cells, with A549 cells exhibiting a more profound transition to a mesenchymal phenotype. TGFβ 1 overexpression in the lungs of mice resulted in an early increase in mesenchymal cell markers and apoptotic genes that preceded collagen deposition, suggesting an early epithelial injury triggers the downstream fibrotic response. In contrast, bleomycin had a gradual increase in mesenchymal cell marker and a decrease in E-cadherin expression that correlated with collagen protein deposition. Finally, we compared normal healthy lung tissue with surgical lung biopsies from IPF patients and observed alterations in epithelial and mesenchymal cell markers, as well as an increase in the apoptotic marker GSK3β. Interestingly, the mesenchymal changes were more profound in rapidly progressive patients in comparison to IPF patients with slowing progressing disease. In summary, this study provides evidence of alterations in epithelial and mesenchymal markers in experimental models of lung fibrosis and how these findings are relevant to clinical disease.

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A Micro RNA Processing Defect in Rapidly Progressing Idiopathic Pulmonary Fibrosis

Cited by 126 publications

References 63 publications

Future Directions in Idiopathic Pulmonary Fibrosis Research. An NHLBI Workshop Report

Future Directions in Idiopathic Pulmonary Fibrosis Research. An NHLBI Workshop Report

Common pathways in idiopathic pulmonary fibrosis and cancer

An Assessment of Epithelial and Mesenchymal Phenotypes in Experimental and Clinical Pulmonary Fibrosis

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