MiR-1343 Attenuates Pathways of Fibrosis by Targeting the TGF-β Receptors

Overview

Journal Biochem J

Specialty Biochemistry

Date 2015 Nov 7

PMID 26542979

Citations 41

Authors

Lindsay R Stolzenburg

Sarah Wachtel

Hong Dang

Ann Harris

Affiliations

Soon will be listed here.

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.

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