Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2012:6:130-9.
doi: 10.2174/1874312901206010130. Epub 2012 Jun 15.

Role of MicroRNAs in Fibrosis

Serena Vettori  1 , Steffen Gay, Oliver Distler
Affiliations

Role of MicroRNAs in Fibrosis

Serena Vettori et al. Open Rheumatol J. 2012.

Abstract

Fibrosis is the leading cause of organ dysfunction in diseases such as systemic sclerosis, liver cirrhosis, cardiac fibrosis, progressive kidney disease, and idiopathic pulmonary fibrosis. The hallmark of fibrosis is tissue remodeling with excess deposition of extracellular matrix components, predominantly collagens. Different cell types, cytokines, growth factors, and enzymes interact in complex pathogenic networks with myofibroblasts playing a pivotal role. MicroRNAs are small non-coding RNAs acting as negative regulators of gene expression at the post-transcriptional level. MicroRNAs have been associated with many basic cellular processes as well as with a wide spectrum of diseases, most notably cancer. This review provides a comprehensive overview of microRNAs regulating profibrotic pathways and extracellular matrix synthesis. The potential of miRNA for _targeted therapeutic approaches in fibrotic disorders is also discussed.

Keywords: Fibrosis; antagomirs.; connective tissue growth factor (CTGF); epithelial-to-mesenchymal transition (EMT); extracellular matrix (ECM); fibroblasts; microRNA (miRNA)-mediated gene regulation regulation; signaling pathways; transforming growth factor-beta (TGF-β).

PubMed Disclaimer

Figures

Fig. (1)
Fig. (1)
Schematic miRNA biogenesis and regulation. The miRNA gene is transcribed (pri-miRNA) and cut in the nucleus to generate pre-miRNA. Pre-miRNA is transported to the cytoplasm and is further processed there. Mature miRNA is originated as a mature miRNA:miRNA* (passenger strand) duplex. Mature miRNA is incorporated in RISC to bind a _target mRNA. Perfect miRNA-mRNA binding leads to mRNA cleavage, while imperfect miRNA-mRNA binding leads to translational repression (rarely to translational stimulation). Levels of cellular bioactive miRNA can be controlled by both transcriptional regulation, including epigenetic modifications and _target-dependent loops, and post-transcriptional regulation, including decoy mechanisms exerted by pseudogenes, and intercellular exosomedependent trafficking. DNMTs = DNA methyltransferases; HDACs = histone deacetylases; DGCR8 = DiGeorge syndrome critical region 8; RISC = RNA-induced silencing complex; ψ = pseudogene.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Wynn TA. Cellular and molecular mechanisms of fibrosis. J Pathol . 2007;214:199–210. - PMC - PubMed
    1. Wynn TA. Common and unique mechanisms regulate fibrosis in various fibroproliferative diseases. J Clin Invest. 2007;117:524–9. - PMC - PubMed
    1. Zimmer V, Lammert F. Genetics in liver disease: new concepts. Curr Opin Gastroenterol. 2011;27:231–9. - PubMed
    1. Romano E, Manetti M, Guiducci S, Ceccarelli C, Allanore Y, Matucci CM. The genetics of systemic sclerosis: an update. Clin Exp Rheumatol. 2011;29:S75–86. - PubMed
    1. Tomasek JJ, Gabbiani G, Hinz B, Chaponnier C, Brown RA. Myofibroblasts and mechano-regulation of connective tissue remodeling. Nat Rev Mol Cell Biol. 2002;3:349–63. - PubMed

LinkOut - more resources

  NODES
twitter 2