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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Research Article| January 25 2016
miR-1343 attenuates pathways of fibrosis by targeting the TGF-β receptors
Lindsay R. Stolzenburg ;
Sarah Wachtel ;
Hong Dang ;
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 email@example.com).
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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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