No Cover Image

Journal article 350 views 247 downloads

The role of microRNA-155/LXR pathway in experimental and Idiopathic Pulmonary Fibrosis / Mariola Kurowska-Stolarska; Manhl K. Hasoo; David J. Welsh; Lynn Stewart; Donna McIntyre; Brian E. Morton; Steven Johnstone; Ashley M. Miller; Darren L. Asquith; Neal L. Millar; Ann B. Millar; Carol A. Feghali-Bostwick; Nikhil Hirani; Peter J. Crick; Yuqin Wang; William J. Griffiths; Iain B. McInnes; Charles McSharry

Journal of Allergy and Clinical Immunology

Swansea University Author: Griffiths, William

Abstract

AbstractBackground: Idiopathic Pulmonary Fibrosis (IPF) is progressive and rapidly fatal. Improved understanding of pathogenesis is required to prosper novel therapeutics. Epigenetic changes contribute to IPF therefore microRNAs may reveal novel pathogenic pathways.Objectives: To determine the regul...

Full description

Published in: Journal of Allergy and Clinical Immunology
ISSN: 00916749
Published: 2016
Online Access: Check full text

URI: https://cronfa.swan.ac.uk/Record/cronfa30591
Tags: Add Tag
No Tags, Be the first to tag this record!
first_indexed 2016-10-14T18:54:58Z
last_indexed 2019-07-15T14:42:37Z
id cronfa30591
recordtype SURis
fullrecord <?xml version="1.0"?><rfc1807><datestamp>2019-07-15T11:53:24Z</datestamp><bib-version>v2</bib-version><id>30591</id><entry>2016-10-14</entry><title>The role of microRNA-155/LXR pathway in experimental and Idiopathic Pulmonary Fibrosis</title><alternativeTitle></alternativeTitle><author>William Griffiths</author><firstname>William</firstname><surname>Griffiths</surname><active>true</active><ORCID>0000-0002-4129-6616</ORCID><ethesisStudent>false</ethesisStudent><sid>3316b1d1b524be1831790933eed1c26e</sid><email>3e4851c27dfd9cf65adbd476d1f7a3bf</email><emailaddr>zaxgD1SlXhR1pE5DoDi9bR8j7kl4zZwebz0wEHEQAUk=</emailaddr><date>2016-10-14</date><deptcode>BMS</deptcode><abstract>AbstractBackground: Idiopathic Pulmonary Fibrosis (IPF) is progressive and rapidly fatal. Improved understanding of pathogenesis is required to prosper novel therapeutics. Epigenetic changes contribute to IPF therefore microRNAs may reveal novel pathogenic pathways.Objectives: To determine the regulatory role of microRNA(miR)-155 in the pro-fibrotic function of murine lung macrophages and fibroblasts, IPF lung fibroblasts and its contribution to experimental pulmonary fibrosis.Methods: Bleomycin-induced lung fibrosis in wild-type and miR-155-/- mice was analyzed by histology, collagen and pro-fibrotic gene expression. Mechanisms were identified by in silico and molecular approaches; validated in mouse lung fibroblasts and macrophages, and in IPF lung fibroblasts, using loss-and-gain of function assays, and in vivo using specific inhibitors.Results: miR-155-/- mice developed exacerbated lung fibrosis, increased collagen deposition, collagen 1 and 3 mRNA expression, TGF&#x3B2; production, and activation of alternatively-activated macrophages, contributed by deregulation of the microRNA-155 target gene the liver X receptor (LXR)&#x3B1; in lung fibroblasts and macrophages. Inhibition of LXR&#x3B1; in experimental lung fibrosis and in IPF lung fibroblasts reduced the exacerbated fibrotic response. Similarly, enforced expression of miR-155 reduced the pro-fibrotic phenotype of IPF and miR-155-/- fibroblasts.Conclusion: We describe herein a molecular pathway comprising miR-155 and its epigenetic LXR&#x3B1; target that when deregulated enables pathogenic pulmonary fibrosis. Manipulation of the miR-155/LXR pathway may have therapeutic potential for IPF.</abstract><type>Journal article</type><journal>Journal of Allergy and Clinical Immunology</journal><volume/><journalNumber/><paginationStart/><paginationEnd/><publisher></publisher><placeOfPublication/><isbnPrint/><isbnElectronic/><issnPrint>00916749</issnPrint><issnElectronic/><keywords>microRNA-155, lung fibrosis, Liver X Receptor, fibroblasts, alternatively activated macrophages</keywords><publishedDay>0</publishedDay><publishedMonth>0</publishedMonth><publishedYear>2016</publishedYear><publishedDate>2016-01-01</publishedDate><doi>10.1016/j.jaci.2016.09.021</doi><url></url><notes>The Swansea University team provided expert knowledge of LXR activity and generated the data presented in Supplemental Table E6</notes><college>Swansea University Medical School</college><department/><CollegeCode>CMED</CollegeCode><DepartmentCode>BMS</DepartmentCode><institution/><researchGroup>Biomarkers and genes</researchGroup><supervisor/><sponsorsfunders>RCUK, BBSRC, BB/I001735/1, BB/L001942/1</sponsorsfunders><grantnumber/><degreelevel/><degreename>None</degreename><lastEdited>2019-07-15T11:53:24Z</lastEdited><Created>2016-10-14T15:42:22Z</Created><path><level id="1">Swansea University Medical School</level><level id="2">Medicine</level></path><authors><author><firstname>Mariola</firstname><surname>Kurowska-Stolarska</surname><orcid/><order>1</order></author><author><firstname>Manhl K.</firstname><surname>Hasoo</surname><orcid/><order>2</order></author><author><firstname>David J.</firstname><surname>Welsh</surname><orcid/><order>3</order></author><author><firstname>Lynn</firstname><surname>Stewart</surname><orcid/><order>4</order></author><author><firstname>Donna</firstname><surname>McIntyre</surname><orcid/><order>5</order></author><author><firstname>Brian E.</firstname><surname>Morton</surname><orcid/><order>6</order></author><author><firstname>Steven</firstname><surname>Johnstone</surname><orcid/><order>7</order></author><author><firstname>Ashley M.</firstname><surname>Miller</surname><orcid/><order>8</order></author><author><firstname>Darren L.</firstname><surname>Asquith</surname><orcid/><order>9</order></author><author><firstname>Neal L.</firstname><surname>Millar</surname><orcid/><order>10</order></author><author><firstname>Ann B.</firstname><surname>Millar</surname><orcid/><order>11</order></author><author><firstname>Carol A.</firstname><surname>Feghali-Bostwick</surname><orcid/><order>12</order></author><author><firstname>Nikhil</firstname><surname>Hirani</surname><orcid/><order>13</order></author><author><firstname>Peter J.</firstname><surname>Crick</surname><orcid/><order>14</order></author><author><firstname>Yuqin</firstname><surname>Wang</surname><orcid/><order>15</order></author><author><firstname>William J.</firstname><surname>Griffiths</surname><orcid/><order>16</order></author><author><firstname>Iain B.</firstname><surname>McInnes</surname><orcid/><order>17</order></author><author><firstname>Charles</firstname><surname>McSharry</surname><orcid/><order>18</order></author></authors><documents><document><filename>0030591-09012017144438.pdf</filename><originalFilename>Griffiths.1-s2.0-S0091674916311320-main.pdf</originalFilename><uploaded>2017-01-09T14:44:38Z</uploaded><type>Output</type><contentLength>2298017</contentLength><contentType>application/pdf</contentType><version>P</version><cronfaStatus>true</cronfaStatus><action>Published to Cronfa</action><actionDate>09/01/2017</actionDate><embargoDate>2017-01-09T00:00:00</embargoDate><documentNotes>Distributed under the terms of a CC-BY license.</documentNotes><copyrightCorrect>false</copyrightCorrect><language/></document></documents></rfc1807>
spelling 2019-07-15T11:53:24Z v2 30591 2016-10-14 The role of microRNA-155/LXR pathway in experimental and Idiopathic Pulmonary Fibrosis William Griffiths William Griffiths true 0000-0002-4129-6616 false 3316b1d1b524be1831790933eed1c26e 3e4851c27dfd9cf65adbd476d1f7a3bf zaxgD1SlXhR1pE5DoDi9bR8j7kl4zZwebz0wEHEQAUk= 2016-10-14 BMS AbstractBackground: Idiopathic Pulmonary Fibrosis (IPF) is progressive and rapidly fatal. Improved understanding of pathogenesis is required to prosper novel therapeutics. Epigenetic changes contribute to IPF therefore microRNAs may reveal novel pathogenic pathways.Objectives: To determine the regulatory role of microRNA(miR)-155 in the pro-fibrotic function of murine lung macrophages and fibroblasts, IPF lung fibroblasts and its contribution to experimental pulmonary fibrosis.Methods: Bleomycin-induced lung fibrosis in wild-type and miR-155-/- mice was analyzed by histology, collagen and pro-fibrotic gene expression. Mechanisms were identified by in silico and molecular approaches; validated in mouse lung fibroblasts and macrophages, and in IPF lung fibroblasts, using loss-and-gain of function assays, and in vivo using specific inhibitors.Results: miR-155-/- mice developed exacerbated lung fibrosis, increased collagen deposition, collagen 1 and 3 mRNA expression, TGFβ production, and activation of alternatively-activated macrophages, contributed by deregulation of the microRNA-155 target gene the liver X receptor (LXR)α in lung fibroblasts and macrophages. Inhibition of LXRα in experimental lung fibrosis and in IPF lung fibroblasts reduced the exacerbated fibrotic response. Similarly, enforced expression of miR-155 reduced the pro-fibrotic phenotype of IPF and miR-155-/- fibroblasts.Conclusion: We describe herein a molecular pathway comprising miR-155 and its epigenetic LXRα target that when deregulated enables pathogenic pulmonary fibrosis. Manipulation of the miR-155/LXR pathway may have therapeutic potential for IPF. Journal article Journal of Allergy and Clinical Immunology 00916749 microRNA-155, lung fibrosis, Liver X Receptor, fibroblasts, alternatively activated macrophages 0 0 2016 2016-01-01 10.1016/j.jaci.2016.09.021 The Swansea University team provided expert knowledge of LXR activity and generated the data presented in Supplemental Table E6 Swansea University Medical School CMED BMS Biomarkers and genes RCUK, BBSRC, BB/I001735/1, BB/L001942/1 None 2019-07-15T11:53:24Z 2016-10-14T15:42:22Z Swansea University Medical School Medicine Mariola Kurowska-Stolarska 1 Manhl K. Hasoo 2 David J. Welsh 3 Lynn Stewart 4 Donna McIntyre 5 Brian E. Morton 6 Steven Johnstone 7 Ashley M. Miller 8 Darren L. Asquith 9 Neal L. Millar 10 Ann B. Millar 11 Carol A. Feghali-Bostwick 12 Nikhil Hirani 13 Peter J. Crick 14 Yuqin Wang 15 William J. Griffiths 16 Iain B. McInnes 17 Charles McSharry 18 0030591-09012017144438.pdf Griffiths.1-s2.0-S0091674916311320-main.pdf 2017-01-09T14:44:38Z Output 2298017 application/pdf P true Published to Cronfa 09/01/2017 2017-01-09T00:00:00 Distributed under the terms of a CC-BY license. false
title The role of microRNA-155/LXR pathway in experimental and Idiopathic Pulmonary Fibrosis
spellingShingle The role of microRNA-155/LXR pathway in experimental and Idiopathic Pulmonary Fibrosis
Griffiths, William
title_short The role of microRNA-155/LXR pathway in experimental and Idiopathic Pulmonary Fibrosis
title_full The role of microRNA-155/LXR pathway in experimental and Idiopathic Pulmonary Fibrosis
title_fullStr The role of microRNA-155/LXR pathway in experimental and Idiopathic Pulmonary Fibrosis
title_full_unstemmed The role of microRNA-155/LXR pathway in experimental and Idiopathic Pulmonary Fibrosis
title_sort The role of microRNA-155/LXR pathway in experimental and Idiopathic Pulmonary Fibrosis
author_id_str_mv 3316b1d1b524be1831790933eed1c26e
author_id_fullname_str_mv 3316b1d1b524be1831790933eed1c26e_***_Griffiths, William
author Griffiths, William
author2 Mariola Kurowska-Stolarska
Manhl K. Hasoo
David J. Welsh
Lynn Stewart
Donna McIntyre
Brian E. Morton
Steven Johnstone
Ashley M. Miller
Darren L. Asquith
Neal L. Millar
Ann B. Millar
Carol A. Feghali-Bostwick
Nikhil Hirani
Peter J. Crick
Yuqin Wang
William J. Griffiths
Iain B. McInnes
Charles McSharry
format Journal article
container_title Journal of Allergy and Clinical Immunology
publishDate 2016
institution Swansea University
issn 00916749
doi_str_mv 10.1016/j.jaci.2016.09.021
college_str Swansea University Medical School
hierarchytype
hierarchy_top_id swanseauniversitymedicalschool
hierarchy_top_title Swansea University Medical School
hierarchy_parent_id swanseauniversitymedicalschool
hierarchy_parent_title Swansea University Medical School
department_str Medicine{{{_:::_}}}Swansea University Medical School{{{_:::_}}}Medicine
document_store_str 1
active_str 1
researchgroup_str Biomarkers and genes
description AbstractBackground: Idiopathic Pulmonary Fibrosis (IPF) is progressive and rapidly fatal. Improved understanding of pathogenesis is required to prosper novel therapeutics. Epigenetic changes contribute to IPF therefore microRNAs may reveal novel pathogenic pathways.Objectives: To determine the regulatory role of microRNA(miR)-155 in the pro-fibrotic function of murine lung macrophages and fibroblasts, IPF lung fibroblasts and its contribution to experimental pulmonary fibrosis.Methods: Bleomycin-induced lung fibrosis in wild-type and miR-155-/- mice was analyzed by histology, collagen and pro-fibrotic gene expression. Mechanisms were identified by in silico and molecular approaches; validated in mouse lung fibroblasts and macrophages, and in IPF lung fibroblasts, using loss-and-gain of function assays, and in vivo using specific inhibitors.Results: miR-155-/- mice developed exacerbated lung fibrosis, increased collagen deposition, collagen 1 and 3 mRNA expression, TGFβ production, and activation of alternatively-activated macrophages, contributed by deregulation of the microRNA-155 target gene the liver X receptor (LXR)α in lung fibroblasts and macrophages. Inhibition of LXRα in experimental lung fibrosis and in IPF lung fibroblasts reduced the exacerbated fibrotic response. Similarly, enforced expression of miR-155 reduced the pro-fibrotic phenotype of IPF and miR-155-/- fibroblasts.Conclusion: We describe herein a molecular pathway comprising miR-155 and its epigenetic LXRα target that when deregulated enables pathogenic pulmonary fibrosis. Manipulation of the miR-155/LXR pathway may have therapeutic potential for IPF.
published_date 2016-01-01T04:45:31Z
_version_ 1647973007485829120
score 10.892022