miR-142-5p and miR-130a-3p are regulated by IL-4 and IL-13 and control profibrogenic macrophage program

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 I...

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Main Authors:	Su, Shicheng, Zhao, Qiyi, He, Chonghua, Huang, Di, Liu, Jiang, Chen, Fei, Chen, Jianing, Liao, Jian-You, Cui, Xiuying, Zeng, Yunjie, Yao, Herui, Su, Fengxi, Liu, Qiang, Jiang, Shanping, Song, Erwei
Format:	Online
Language:	English
Published:	Nature Pub. Group 2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4600756/

id	pubmed-4600756
recordtype	oai_dc
spelling	pubmed-46007562015-10-21 miR-142-5p and miR-130a-3p are regulated by IL-4 and IL-13 and control profibrogenic macrophage program Su, Shicheng Zhao, Qiyi He, Chonghua Huang, Di Liu, Jiang Chen, Fei Chen, Jianing Liao, Jian-You Cui, Xiuying Zeng, Yunjie Yao, Herui Su, Fengxi Liu, Qiang Jiang, Shanping Song, Erwei Article 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 PPARγ, 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. Nature Pub. Group 2015-10-05 /pmc/articles/PMC4600756/ /pubmed/26436920 http://dx.doi.org/10.1038/ncomms9523 Text en Copyright © 2015, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Su, Shicheng Zhao, Qiyi He, Chonghua Huang, Di Liu, Jiang Chen, Fei Chen, Jianing Liao, Jian-You Cui, Xiuying Zeng, Yunjie Yao, Herui Su, Fengxi Liu, Qiang Jiang, Shanping Song, Erwei
spellingShingle	Su, Shicheng Zhao, Qiyi He, Chonghua Huang, Di Liu, Jiang Chen, Fei Chen, Jianing Liao, Jian-You Cui, Xiuying Zeng, Yunjie Yao, Herui Su, Fengxi Liu, Qiang Jiang, Shanping Song, Erwei miR-142-5p and miR-130a-3p are regulated by IL-4 and IL-13 and control profibrogenic macrophage program
author_facet	Su, Shicheng Zhao, Qiyi He, Chonghua Huang, Di Liu, Jiang Chen, Fei Chen, Jianing Liao, Jian-You Cui, Xiuying Zeng, Yunjie Yao, Herui Su, Fengxi Liu, Qiang Jiang, Shanping Song, Erwei
author_sort	Su, Shicheng
title	miR-142-5p and miR-130a-3p are regulated by IL-4 and IL-13 and control profibrogenic macrophage program
title_short	miR-142-5p and miR-130a-3p are regulated by IL-4 and IL-13 and control profibrogenic macrophage program
title_full	miR-142-5p and miR-130a-3p are regulated by IL-4 and IL-13 and control profibrogenic macrophage program
title_fullStr	miR-142-5p and miR-130a-3p are regulated by IL-4 and IL-13 and control profibrogenic macrophage program
title_full_unstemmed	miR-142-5p and miR-130a-3p are regulated by IL-4 and IL-13 and control profibrogenic macrophage program
title_sort	mir-142-5p and mir-130a-3p are regulated by il-4 and il-13 and control profibrogenic macrophage program
description	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 PPARγ, 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.
publisher	Nature Pub. Group
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4600756/
_version_	1613486282412916736

miR-142-5p and miR-130a-3p are regulated by IL-4 and IL-13 and control profibrogenic macrophage program

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