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.
Abbreviations:
AP-1 (activation protein-1), AT1R (angiotensin II type I receptor), EMT (epithelial mesenchymal transition), HMGA2 (h mobility group AT-hook 2), IGF1 (insulin-like growth factor 1), IL (interleukin), IPF (idiopathic pulmonary fibrosis), LNA (locked nucleic acid), MMP (metalloproteinases), PDCD4 (programmed cell death 4), PTEN (phosphatase and tensin homolog), RECK (reversion-inducing-cysteine-rich protein with kazal motifs), SBE (SMAD binding elements), TGFβ1 (transforming growth factor β1), TIMP3 (tissue inhibitor of metalloproteinases 3), VEGF (vascular endothelial growth factor)To read this article in full you will need to make a payment
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Article info
Publication history
Published online: February 07, 2011
Accepted:
January 18,
2011
Received in revised form:
January 16,
2011
Received:
December 1,
2010
Footnotes
Supported by NIH Grants HL095397, HL101715, and LM009657 and by the Dorothy P. and Richard P. Simmons Endowed Chair for Pulmonary Research.
Identification
Copyright
© 2011 Mosby, Inc. Published by Elsevier Inc. All rights reserved.
