title: miR-1343 attenuates pathways of fibrosis by targeting the TGF-β receptors.
abstract: 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.
authors.affiliation: 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.
authors.forename: Lindsay R
authors.initials: LR
authors.lastname: Stolzenburg
authors.affiliation: 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.
authors.forename: Sarah
authors.initials: S
authors.lastname: Wachtel
authors.affiliation: Marsico Lung Institute, University of North Carolina Cystic Fibrosis Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, U.S.A.
authors.forename: Hong
authors.initials: H
authors.lastname: Dang
authors.affiliation: 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. ann-harris@northwestern.edu.
authors.forename: Ann
authors.initials: A
authors.lastname: Harris
mesh_terms: D020413:3' Untranslated Regions; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D008168:Lung / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011658:Pulmonary Fibrosis / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D051899:Smad2 Protein / Q000235:genetics / Q000378:metabolism; D051900:Smad3 Protein / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; C000608296:MIRN-1343 microRNA, human; D035683:MicroRNAs; D018125:Receptors, Transforming Growth Factor beta; C497782:SMAD2 protein, human; C497790:SMAD3 protein, human; D051899:Smad2 Protein; D051900:Smad3 Protein; D053773:Transforming Growth Factor beta1; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II
keywords: fibrosis; lung; microRNA; transforming growth factor β