Journal
NATURE COMMUNICATIONS
Volume 6, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms9523
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Funding
- Ministry of Science and Technology of China [2011CB504203, SQ2015CB050449]
- Natural Science Foundation of China [81230060, 81472468, 81490750, 81490751, 8141101179, 81442009, 81472467, 81272894, 81202319, 81372819, 81370120]
- Science Foundation of Guangdong Province [2014A030313094, S2012030006287, 2014A03031308, 2014A030313175]
- translational medicine public platform of Guangdong Province [4202037]
- Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes, Sun-Yat-Sen University [KLB09001]
- Key Laboratory of Malignant Tumor Molecular Mechanism and Translational Medicine of Guangzhou Bureau of Science and Information Technology [[2013]163]
- Guangdong Department of Science & Technology Translational Medicine Center grant [2011A080300002]
- Guangzhou Science and Technology Bureau [2014J4100170, 2013J4100059]
- Sun Yat-Sen University [13ykzd14]
- Specialized Research Fund for the Doctoral Program of Higher Education [20120171110075, 20120171120107]
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Macrophages play a pivotal role in tissue fibrogenesis, which underlies the pathogenesis of many end-stage chronic inflammatory diseases. MicroRNAs are key regulators of immune cell functions, but their roles in macrophage's fibrogenesis have not been characterized. Here we show that IL-4 and IL-13 induce miR-142-5p and downregulate miR-130a-3p in macrophages; these changes sustain the profibrogenic effect of macrophages. In vitro, miR-142-5p mimic prolongs STAT6 phosphorylation by targeting its negative regulator, SOCS1. Blocking miR-130a relieves its inhibition of PPAR gamma, which coordinates STAT6 signalling. In vivo, inhibiting miR-142-5p and increasing miR-130a-3p expression with locked nucleic acid-modified oligonucleotides inhibits CCL4-induced liver fibrosis and bleomycin-induced lung fibrosis in mice. Furthermore, macrophages from the tissue samples of patients with liver cirrhosis and idiopathic pulmonary fibrosis display increased miR-142-5p and decreased miR-130a-3p expression. Therefore, miR-142-5p and miR-130a-3p regulate macrophage profibrogenic gene expression in chronic inflammation.
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