miR-29 Is a Major Regulator of Genes Associated with Pulmonary Fibrosis
01 Aug 2011-American Journal of Respiratory Cell and Molecular Biology (American Thoracic Society)-Vol. 45, Iss: 2, pp 287-294
TL;DR: A large-scale screening for miRNAs potentially involved in bleomycin-induced fibrosis found expression of miR-29 family members significantly reduced in fibrotic lungs, and gene expression profiles of human fetal lung fibroblast IMR-90 cells in which endogenous miR -29 was knocked down strongly suggest a role of mi R-29 in the pathogenesis of pulmonary fibrosis.
Abstract: MicroRNAs (miRNA) are small regulatory RNAs that control gene expression by translational suppression and destabilization of target mRNAs. There is increasing evidence that miRNAs regulate genes associated with fibrosis in organs, such as the heart, kidney, liver, and the lung. In a large-scale screening for miRNAs potentially involved in bleomycin-induced fibrosis, we found expression of miR-29 family members significantly reduced in fibrotic lungs. Analysis of normal lungs showed the presence of miR-29 in subsets of interstitial cells of the alveolar wall, pleura, and at the entrance of the alveolar duct, known sites of pulmonary fibrosis. miR-29 levels inversely correlated with the expression levels of profibrotic target genes and the severity of the fibrosis. To study the impact of miR-29 down-regulation in the lung interstitium, we characterized gene expression profiles of human fetal lung fibroblast IMR-90 cells in which endogenous miR-29 was knocked down. This confirmed the derepression of reported miR-29 targets, including several collagens, but also revealed up-regulation of a large number of previously unrecognized extracellular matrix-associated and remodeling genes. Moreover, we found that miR-29 is suppressed by transforming growth factor (TGF)-β1 in these cells, and that many fibrosis-associated genes up-regulated by TGF-β1 are derepressed by miR-29 knockdown. Interestingly, a comparison of TGF-β1 and miR-29 targets revealed that miR-29 controls an additional subset of fibrosis-related genes, including laminins and integrins, independent of TGF-β1. Together, these strongly suggest a role of miR-29 in the pathogenesis of pulmonary fibrosis. miR-29 may be a potential new therapeutic target for this disease.
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TL;DR: In this article, the authors reviewed recent data on the clinical course, therapeutic options, and underlying mechanisms thought to be involved in the pathogenesis of idiopathic pulmonary fibrosis.
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Cites background from "miR-29 Is a Major Regulator of Gene..."
...…(Hill and Olson, 2008). miR-29 is downregulated under conditions of cardiovascular disease associated with fibrosis and excessive ECM production (Boon et al., 2011; Cushing et al., 2011; van Rooij et al., 2008), implicating this miRNA as a repressive mediator of fibrotic disease (Figure 3A)....
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...miR-29 is downregulated under conditions of cardiovascular disease associated with fibrosis and excessive ECM production (Boon et al., 2011; Cushing et al., 2011; van Rooij et al., 2008), implicating this miRNA as a repressive mediator of fibrotic disease (Figure 3A)....
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TL;DR: This review guides the reader through important aspects of non-coding RNA biology, including their biogenesis, mode of actions, physiological function, as well as their role in the disease context (such as in cancer or the cardiovascular system).
Abstract: Advances in RNA-sequencing techniques have led to the discovery of thousands of non-coding transcripts with unknown function. There are several types of non-coding linear RNAs such as microRNAs (miRNA) and long non-coding RNAs (lncRNA), as well as circular RNAs (circRNA) consisting of a closed continuous loop. This review guides the reader through important aspects of non-coding RNA biology. This includes their biogenesis, mode of actions, physiological function, as well as their role in the disease context (such as in cancer or the cardiovascular system). We specifically focus on non-coding RNAs as potential therapeutic targets and diagnostic biomarkers.
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Cites background from "miR-29 Is a Major Regulator of Gene..."
...Knockdown of miR-29 in these cells leads to derepression of extracellular matrix genes and fibrosisrelated genes (54)....
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Cites background from "miR-29 Is a Major Regulator of Gene..."
...Knockdown or TGF 1-mediated down-regulation of miR-29 in cultured lung fibroblast derepressed fibrosis-associated genes.(45) Down-regulation of miR-29 in cardiac fibroblasts in vitro and in vivo induces fibrosis-associated genes, whereas its overexpression has a fibrosis-suppressing effect....
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Journal Article•
TL;DR: Recent data on the clinical course, therapeutic options, and underlying mechanisms thought to be involved in the pathogenesis of idiopathic pulmonary fibrosis are reviewed.
Abstract: Analysis of bronchoalveolar lavage cellular constituents has been recommended as a valuable method for the characterization of the inflammatory cellular population and for studying cellular interactions in the lower respiratory tract of patients with idiopathic pulmonary fibrosis (IPF). However, the clinical relevance of the enumeration of cells in bronchoalveolar lavage fluid (BALF) from patients with IPF remains controversial. We therefore examined the correlations between BALF cellular constituents and both the histopathologic abnormalities and the subsequent clinical response to corticosteroid therapy in 26 newly diagnosed, untreated patients with IPF. The BALF lymphocytosis was associated with moderate-to-severe alveolar septal inflammation (p < 0.0005) and with a relative lack of histologic honeycombing (p < 0.05). On the other hand, BALF neutrophil and eosinophil contents did not significantly correlate with any of eleven particular histopathologic abnormalities, and BALF neutrophil and lymphocyte ...
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