Irreversible respiratory obstruction resulting from progressive airway damage, inflammation and fibrosis is a feature of several chronic respiratory diseases, including cystic fibrosis (CF), idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD). The cytokine transforming growth factor β (TGF-β) has a pivotal role in promoting lung fibrosis and is implicated in respiratory disease severity. In the present study, we show that a previously uncharacterized miRNA, miR-1343, reduces the expression of both TGF-β receptor 1 and 2 by directly targeting their 3′-UTRs. After TGF-β exposure, elevated intracellular miR-1343 significantly decreases levels of activated TGF-β effector molecules, pSMAD2 (phosphorylated SMAD2) and pSMAD3 (phosphorylated SMAD3), when compared with a non-targeting control miRNA. As a result, the abundance of fibrotic markers is reduced, cell migration into a scratch wound impaired and epithelial-to-mesenchymal transition (EMT) repressed. Mature miR-1343 is readily detected in human neutrophils and HL-60 cells and is activated in response to stress in A549 lung epithelial cells. miR-1343 may have direct therapeutic applications in fibrotic lung disease.
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February 2016
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Point scanning confocal microscopic imaging of C2C12 undifferentiatedmyoblasts (top panels) and differentiatedmultinucleated myotubes (bottom panels) immunofluorescently labelled with DAPI (blue) PDLIM7 (green) and Phalloidin or Nedd4-1 (red). Merged images show co-localization of PDLIM7 and Phalloidin decreases with myotube formation (left panels) and co-location of PDLIM7 and Nedd4-1 increases with myotube formation (right panels). Image courtesy of Robert D’Cruz et al. (for further details see pages 267–276). - PDF Icon PDF LinkFront Matter
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Research Article|
January 25 2016
miR-1343 attenuates pathways of fibrosis by targeting the TGF-β receptors
Lindsay R. Stolzenburg;
Lindsay R. Stolzenburg
*Human Molecular Genetics Program, Lurie Children's Research Center, Chicago, IL 60614, U.S.A.
†Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, U.S.A.
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Sarah Wachtel;
Sarah Wachtel
*Human Molecular Genetics Program, Lurie Children's Research Center, Chicago, IL 60614, U.S.A.
†Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, U.S.A.
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Hong Dang;
Hong Dang
‡Marsico Lung Institute, University of North Carolina Cystic Fibrosis Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, U.S.A.
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Ann Harris
Ann Harris
1
*Human Molecular Genetics Program, Lurie Children's Research Center, Chicago, IL 60614, U.S.A.
†Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, U.S.A.
§Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, U.S.A.
1To whom correspondence should be addressed (email ann-harris@northwestern.edu).
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Publisher: Portland Press Ltd
Received:
July 21 2015
Revision Received:
November 02 2015
Accepted:
November 05 2015
Accepted Manuscript online:
November 05 2015
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© 2016 Authors; published by Portland Press Limited
2016
Biochem J (2016) 473 (3): 245–256.
Article history
Received:
July 21 2015
Revision Received:
November 02 2015
Accepted:
November 05 2015
Accepted Manuscript online:
November 05 2015
Citation
Lindsay R. Stolzenburg, Sarah Wachtel, Hong Dang, Ann Harris; miR-1343 attenuates pathways of fibrosis by targeting the TGF-β receptors. Biochem J 1 February 2016; 473 (3): 245–256. doi: https://doi.org/10.1042/BJ20150821
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