MicroRNAs in idiopathic pulmonary fibrosis

Abstract

In this review, we describe the recent advances in the understanding of the role of microRNAs in idiopathic pulmonary fibrosis (IPF), a chronic progressive and lethal fibrotic lung disease. Approximately 10% of the microRNAs are significantly changed in IPF lungs. Among the significantly downregulated microRNAs are members of let-7, mir-29, and mir-30 families as well as miR-17∼92 cluster among the upregulated mir-155 and mir-21. Downregulation of let-7 family members leads to changes consistent with epithelial mesenchymal transition in lung epithelial cells both in vitro and in vivo, whereas inhibition of mir-21 modulates fibrosis in the bleomycin model of lung fibrosis. Perturbations of mir-155 and mir-29 have profibrotic effects in vitro but have not yet been assessed in vivo in the context of lung fibrosis. A recurrent global theme is that many microRNAs studied in IPF are both regulated by transforming growth factor β1 (TGFβ1) and regulate TGFβ1 signaling pathway by their target genes. As a result, their aberrant expression leads to a release of inhibitions on the TGFβ1 pathway and to the creation of feed-forward loops. Coanalysis of published microRNA and gene expression microarray data in IPF reveals enrichment of the TGFβ1, Wnt, sonic hedgehog, p53, and vascular endothelial growth factor pathways and complex regulatory networks. The changes in microRNA expression in the IPF lung and the evidence for their role in the fibrosis suggest that microRNAs should be evaluated as therapeutic targets in IPF.

Key Role of MicroRNA in the Regulation of Granulocyte Macrophage Colony-stimulating Factor Expression in Murine Alveolar Epithelial Cells during Oxidative Stress

“…In particular, Let7 family members are expressed in relative abundance and are postulated to play a role in pulmonary fibrosis (37). Interestingly, Let7 was identified in our microarray experiments as induced by hyperoxia and suppressed by treatment with recombinant GM-CSF during hyperoxia; however, Let7 does not appear to target GM-CSF 3Ј-UTR directly.…”

Epigenetic and Transcriptomic Regulation of Lung Repair during Recovery from Influenza Infection

“…18,19 Considering the lung pathologic process associated with the resolution from influenza infection and the dramatic changes in the lung transcriptome, we examined the impact of influenza infection on miRNA expression in the lung 21 days after infection. Mice were infected with influenza A/PR/8/34 (H1N1) or PBS vehicle for 21 days, and miRNA microarray was performed.…”

miRNA Control of Tissue Repair and Regeneration

“…78 In adults, members of the miR-29 family cause suppression of ECM genes, resulting in tissue repair with a scar. Dysregulation of ECM caused by lower miR-29 is associated with fibrosis development in several organs, including the heart, 77 kidney, 79 lung, 80 and liver. 81 Furthermore, miR-29 influences tissue differentiation and senescence.…”