A microRNA-21-mediated SATB1/S100A9/NF-κB axis promotes chronic obstructive pulmonary disease pathogenesis
Chronic obstructive pulmonary disease (COPD) is the third leading cause of morbidity and death worldwide. Inhalation of cigarette smoke (CS) is the major cause in developed countries. Current therapies have limited efficacy in controlling disease or halting its progression. Aberrant expression of mi...
Saved in:
Published in | Science translational medicine Vol. 13; no. 621; p. eaav7223 |
---|---|
Main Authors | , , , , , , , , , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
24.11.2021
|
Subjects | |
Online Access | Get more information |
Cover
Loading…
Abstract | Chronic obstructive pulmonary disease (COPD) is the third leading cause of morbidity and death worldwide. Inhalation of cigarette smoke (CS) is the major cause in developed countries. Current therapies have limited efficacy in controlling disease or halting its progression. Aberrant expression of microRNAs (miRNAs) is associated with lung disease, including COPD. We performed miRNA microarray analyses of the lungs of mice with CS-induced experimental COPD. miR-21 was the second highest up-regulated miRNA, particularly in airway epithelium and lung macrophages. Its expression in human lung tissue correlated with reduced lung function in COPD. Prophylactic and therapeutic treatment with a specific miR-21 inhibitor (Ant-21) inhibited CS-induced lung miR-21 expression in mice; suppressed airway macrophages, neutrophils, and lymphocytes; and improved lung function, as evidenced by decreased lung hysteresis, transpulmonary resistance, and tissue damping in mouse models of COPD. In silico analyses identified a potential miR-21/special AT-rich sequence–binding protein 1 (SATB1)/S100 calcium binding protein A9 (S100A9)/nuclear factor κB (NF-κB) axis, which was further investigated. CS exposure reduced lung SATB1 in a mouse model of COPD, whereas Ant-21 treatment restored SATB1 and reduced S100A9 expression and NF-κB activity. The beneficial effects of Ant-21 in mice were reversed by treatment with SATB1-targeting small interfering RNA. We have identified a pathogenic role for a miR-21/SATB1/S100A9/NF-κB axis in COPD and defined miR-21 as a therapeutic target for this disease. |
---|---|
AbstractList | Chronic obstructive pulmonary disease (COPD) is the third leading cause of morbidity and death worldwide. Inhalation of cigarette smoke (CS) is the major cause in developed countries. Current therapies have limited efficacy in controlling disease or halting its progression. Aberrant expression of microRNAs (miRNAs) is associated with lung disease, including COPD. We performed miRNA microarray analyses of the lungs of mice with CS-induced experimental COPD. miR-21 was the second highest up-regulated miRNA, particularly in airway epithelium and lung macrophages. Its expression in human lung tissue correlated with reduced lung function in COPD. Prophylactic and therapeutic treatment with a specific miR-21 inhibitor (Ant-21) inhibited CS-induced lung miR-21 expression in mice; suppressed airway macrophages, neutrophils, and lymphocytes; and improved lung function, as evidenced by decreased lung hysteresis, transpulmonary resistance, and tissue damping in mouse models of COPD. In silico analyses identified a potential miR-21/special AT-rich sequence–binding protein 1 (SATB1)/S100 calcium binding protein A9 (S100A9)/nuclear factor κB (NF-κB) axis, which was further investigated. CS exposure reduced lung SATB1 in a mouse model of COPD, whereas Ant-21 treatment restored SATB1 and reduced S100A9 expression and NF-κB activity. The beneficial effects of Ant-21 in mice were reversed by treatment with SATB1-targeting small interfering RNA. We have identified a pathogenic role for a miR-21/SATB1/S100A9/NF-κB axis in COPD and defined miR-21 as a therapeutic target for this disease. |
Author | Liu, Gang Kim, Richard Y Donovan, Chantal Ieni, Antonio Hansbro, Philip M Jarnicki, Andrew G Wijnant, Sara Ferguson, Angela L Foster, Paul S Hsu, Alan C Horvat, Jay C Bracke, Ken R Conickx, Griet Ricciardolo, Fabio Lm Mestdagh, Pieter Haw, Tatt Jhong Caramori, Gaetano Wark, Peter A Palendira, Umamainthan Brusselle, Guy G Galvão, Izabela Beckett, Emma L Sunkara, Krishna P Di Stefano, Antonino |
Author_xml | – sequence: 1 givenname: Richard Y orcidid: 0000-0002-8709-5270 surname: Kim fullname: Kim, Richard Y organization: Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute and University of Newcastle, Newcastle, New South Wales 2308, Australia – sequence: 2 givenname: Krishna P orcidid: 0000-0003-3412-0708 surname: Sunkara fullname: Sunkara, Krishna P organization: Intensive Care Unit, John Hunter Hospital, Newcastle, New South Wales 2308, Australia – sequence: 3 givenname: Ken R orcidid: 0000-0001-5906-4605 surname: Bracke fullname: Bracke, Ken R organization: Laboratory for Translational Research in Obstructive Pulmonary Diseases, Department of Respiratory Medicine, Ghent University Hospital, Ghent 9000, Belgium – sequence: 4 givenname: Andrew G surname: Jarnicki fullname: Jarnicki, Andrew G organization: Department of Biochemistry and Pharmacology, University of Melbourne, Victoria 3010, Australia – sequence: 5 givenname: Chantal orcidid: 0000-0003-4558-329X surname: Donovan fullname: Donovan, Chantal organization: Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute and University of Newcastle, Newcastle, New South Wales 2308, Australia – sequence: 6 givenname: Alan C orcidid: 0000-0002-6640-0846 surname: Hsu fullname: Hsu, Alan C organization: Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute and University of Newcastle, Newcastle, New South Wales 2308, Australia – sequence: 7 givenname: Antonio surname: Ieni fullname: Ieni, Antonio organization: Department of Human Pathology in Adult and Developmental Age "Gaetano Barresi", Section of Anatomic Pathology, University of Messina, Messina 98100, Italy – sequence: 8 givenname: Emma L orcidid: 0000-0002-8888-3789 surname: Beckett fullname: Beckett, Emma L organization: Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute and University of Newcastle, Newcastle, New South Wales 2308, Australia – sequence: 9 givenname: Izabela orcidid: 0000-0002-9943-8349 surname: Galvão fullname: Galvão, Izabela organization: Centre for Inflammation, Centenary Institute and University of Technology Sydney, Sydney, New South Wales 2007, Australia – sequence: 10 givenname: Sara surname: Wijnant fullname: Wijnant, Sara organization: Laboratory for Translational Research in Obstructive Pulmonary Diseases, Department of Respiratory Medicine, Ghent University Hospital, Ghent 9000, Belgium – sequence: 11 givenname: Fabio Lm orcidid: 0000-0003-1826-5018 surname: Ricciardolo fullname: Ricciardolo, Fabio Lm organization: Rare Lung Disease Unit, Department of Clinical and Biological Sciences, University of Torino, San Luigi Gonzaga University Hospital Orbassano, Torino 10043, Italy – sequence: 12 givenname: Antonino orcidid: 0000-0003-3479-0875 surname: Di Stefano fullname: Di Stefano, Antonino organization: Istituti Clinici Scientifici Maugeri, IRCCS, SpA Società Benefit, Divisione di Pneumologia e Laboratorio di Citoimmunopatologia dell'Apparato Cardio Respiratorio, Veruno, Novara 28100, Italy – sequence: 13 givenname: Tatt Jhong orcidid: 0000-0003-2315-7089 surname: Haw fullname: Haw, Tatt Jhong organization: Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute and University of Newcastle, Newcastle, New South Wales 2308, Australia – sequence: 14 givenname: Gang orcidid: 0000-0002-0489-2638 surname: Liu fullname: Liu, Gang organization: Centre for Inflammation, Centenary Institute and University of Technology Sydney, Sydney, New South Wales 2007, Australia – sequence: 15 givenname: Angela L orcidid: 0000-0001-5974-0423 surname: Ferguson fullname: Ferguson, Angela L organization: Centenary Institute and University of Technology Sydney, Sydney, New South Wales 2006, Australia – sequence: 16 givenname: Umamainthan orcidid: 0000-0002-1113-3306 surname: Palendira fullname: Palendira, Umamainthan organization: Charles Perkins Centre, University of Sydney, Sydney, New South Wales 2006, Australia – sequence: 17 givenname: Peter A orcidid: 0000-0001-5676-6126 surname: Wark fullname: Wark, Peter A organization: Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute and University of Newcastle, Newcastle, New South Wales 2308, Australia – sequence: 18 givenname: Griet orcidid: 0000-0002-9475-8749 surname: Conickx fullname: Conickx, Griet organization: Ablynx N.V., a Sanofi company, Ghent 9052, Belgium – sequence: 19 givenname: Pieter orcidid: 0000-0001-7821-9684 surname: Mestdagh fullname: Mestdagh, Pieter organization: Center for Medical Genetics and Cancer Research Institute Ghent (CRIG), Ghent University, Ghent 9000, Belgium – sequence: 20 givenname: Guy G orcidid: 0000-0001-7021-8505 surname: Brusselle fullname: Brusselle, Guy G organization: Laboratory for Translational Research in Obstructive Pulmonary Diseases, Department of Respiratory Medicine, Ghent University Hospital, Ghent 9000, Belgium – sequence: 21 givenname: Gaetano orcidid: 0000-0002-9807-327X surname: Caramori fullname: Caramori, Gaetano organization: Pneumologia, Dipartimento di Scienze Biomediche, Odontoiatriche e delle Immagini Morfologiche e Funzionali (BIOMORF), Università di Messina, Messina 98100, Italy – sequence: 22 givenname: Paul S orcidid: 0000-0002-0827-8299 surname: Foster fullname: Foster, Paul S organization: Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute and University of Newcastle, Newcastle, New South Wales 2308, Australia – sequence: 23 givenname: Jay C surname: Horvat fullname: Horvat, Jay C organization: Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute and University of Newcastle, Newcastle, New South Wales 2308, Australia – sequence: 24 givenname: Philip M orcidid: 0000-0002-4741-3035 surname: Hansbro fullname: Hansbro, Philip M organization: Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute and University of Newcastle, Newcastle, New South Wales 2308, Australia |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/34818056$$D View this record in MEDLINE/PubMed |
BookMark | eNo1j-1KwzAYhYMo7kPvQCQ30C1v0qTtz244FcYEN3-PfLxz0bUpTTf01rwIr8mC-uvAgfNwnhE5r0ONhNwAmwBwNY3Wd62u46FCN9H6lHEuzsgQilQliqd8QEYxvjGmciHVJRmINIecSTUk7yWtvG3D86pMOCT93usOHV2XmxlM18BYWUxXi-T7a0b1h4-0aUMVOozU7ttQe0uDiV17tJ0_IW2OhyrUuv2kzkfUsW90tw-vWGP08Ypc7PQh4vVfjsnL4m4zf0iWT_eP83KZWCFkl1jIRSYLt0NwmdvlTDubiizVBWqwGiUgGJ4Lg0YVJlMSlRKpybkCK4EZPia3v9zmaHqhbdP6qv-0_bfmP7YGXeI |
CitedBy_id | crossref_primary_10_1631_jzus_B2300455 crossref_primary_10_1038_d41573_021_00199_0 crossref_primary_10_1002_tox_24132 crossref_primary_10_3390_cancers15010054 crossref_primary_10_1038_s41420_023_01396_z crossref_primary_10_1111_all_15977 crossref_primary_10_1183_13993003_01506_2022 crossref_primary_10_3390_biomedicines11123109 crossref_primary_10_1016_j_snb_2022_132896 crossref_primary_10_1165_rcmb_2022_0338ED crossref_primary_10_1016_j_cej_2023_144800 crossref_primary_10_18332_tid_171357 crossref_primary_10_1016_j_jaci_2024_02_022 crossref_primary_10_2147_COPD_S354634 crossref_primary_10_1016_j_intimp_2023_110990 crossref_primary_10_1016_j_lfs_2024_122715 crossref_primary_10_1016_j_ymthe_2023_06_010 crossref_primary_10_3390_toxics11090749 crossref_primary_10_1186_s12931_022_02069_8 crossref_primary_10_18332_tid_186404 crossref_primary_10_1152_ajplung_00244_2023 crossref_primary_10_1183_13993003_01431_2021 crossref_primary_10_1165_rcmb_2021_0518ED crossref_primary_10_1016_j_celrep_2023_112525 crossref_primary_10_1016_j_intimp_2024_112466 crossref_primary_10_1007_s00432_022_03967_6 crossref_primary_10_3389_fimmu_2022_1085551 crossref_primary_10_3390_cells11203318 crossref_primary_10_1016_j_arabjc_2023_105077 crossref_primary_10_1038_s41467_023_42913_z crossref_primary_10_1186_s12931_024_02726_0 crossref_primary_10_3389_fmicb_2022_934716 crossref_primary_10_1016_j_biopha_2023_114519 crossref_primary_10_1016_j_jaci_2022_04_032 crossref_primary_10_1016_j_ncrna_2024_06_005 crossref_primary_10_1186_s12885_023_11630_7 crossref_primary_10_1016_j_apr_2023_101719 crossref_primary_10_1002_ctm2_1228 crossref_primary_10_2478_jtim_2023_0007 crossref_primary_10_23736_S0026_4806_22_07972_1 crossref_primary_10_1002_smll_202307067 crossref_primary_10_3389_fimmu_2022_968991 crossref_primary_10_1186_s12931_024_02736_y crossref_primary_10_1186_s12931_022_02298_x crossref_primary_10_3892_mmr_2024_13158 crossref_primary_10_1152_ajplung_00232_2022 crossref_primary_10_1016_j_ejphar_2023_175965 crossref_primary_10_3390_ijms24032859 crossref_primary_10_23736_S0026_4806_22_07927_7 crossref_primary_10_1186_s12890_023_02540_2 crossref_primary_10_1007_s12010_023_04773_7 crossref_primary_10_1186_s12931_024_02696_3 crossref_primary_10_1016_j_scitotenv_2023_163073 |
ContentType | Journal Article |
DBID | CGR CUY CVF ECM EIF NPM |
DOI | 10.1126/scitranslmed.aav7223 |
DatabaseName | Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed |
DatabaseTitle | MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) |
DatabaseTitleList | MEDLINE |
Database_xml | – sequence: 1 dbid: NPM name: PubMed url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: EIF name: MEDLINE url: https://proxy.k.utb.cz/login?url=https://www.webofscience.com/wos/medline/basic-search sourceTypes: Index Database |
DeliveryMethod | no_fulltext_linktorsrc |
Discipline | Medicine |
EISSN | 1946-6242 |
ExternalDocumentID | 34818056 |
Genre | Research Support, Non-U.S. Gov't Journal Article |
GroupedDBID | --- 0R~ 4.4 53G 7~K ABJNI ACGFS AENEX AJGZS AJWWR ALMA_UNASSIGNED_HOLDINGS BKF C45 CGR CUY CVF DU5 EBS ECM EIF EMOBN F5P HZ~ NPM O9- OFXIZ OVD OVIDX P2P RHI TEORI |
ID | FETCH-LOGICAL-c335t-c183759dfe1d7df80adc4374a9ea1cae51e1b283beb69b765e6634b8261c510b2 |
IngestDate | Thu May 23 23:35:21 EDT 2024 |
IsDoiOpenAccess | false |
IsOpenAccess | true |
IsPeerReviewed | true |
IsScholarly | true |
Issue | 621 |
Language | English |
LinkModel | OpenURL |
MergedId | FETCHMERGED-LOGICAL-c335t-c183759dfe1d7df80adc4374a9ea1cae51e1b283beb69b765e6634b8261c510b2 |
ORCID | 0000-0002-0489-2638 0000-0001-7821-9684 0000-0001-7021-8505 0000-0002-9943-8349 0000-0003-4558-329X 0000-0002-9475-8749 0000-0001-5676-6126 0000-0003-3412-0708 0000-0002-4741-3035 0000-0002-8888-3789 0000-0002-0827-8299 0000-0003-1826-5018 0000-0001-5974-0423 0000-0002-9807-327X 0000-0002-8709-5270 0000-0001-5906-4605 0000-0003-3479-0875 0000-0003-2315-7089 0000-0002-6640-0846 0000-0002-1113-3306 |
PMID | 34818056 |
ParticipantIDs | pubmed_primary_34818056 |
PublicationCentury | 2000 |
PublicationDate | 2021-11-24 |
PublicationDateYYYYMMDD | 2021-11-24 |
PublicationDate_xml | – month: 11 year: 2021 text: 2021-11-24 day: 24 |
PublicationDecade | 2020 |
PublicationPlace | United States |
PublicationPlace_xml | – name: United States |
PublicationTitle | Science translational medicine |
PublicationTitleAlternate | Sci Transl Med |
PublicationYear | 2021 |
SSID | ssj0068356 |
Score | 2.6043334 |
Snippet | Chronic obstructive pulmonary disease (COPD) is the third leading cause of morbidity and death worldwide. Inhalation of cigarette smoke (CS) is the major cause... |
SourceID | pubmed |
SourceType | Index Database |
StartPage | eaav7223 |
SubjectTerms | Animals Calgranulin B - genetics Calgranulin B - metabolism Lung - pathology Matrix Attachment Region Binding Proteins - genetics Matrix Attachment Region Binding Proteins - metabolism Mice MicroRNAs - genetics MicroRNAs - metabolism NF-kappa B - metabolism Pulmonary Disease, Chronic Obstructive - genetics Pulmonary Disease, Chronic Obstructive - metabolism |
Title | A microRNA-21-mediated SATB1/S100A9/NF-κB axis promotes chronic obstructive pulmonary disease pathogenesis |
URI | https://www.ncbi.nlm.nih.gov/pubmed/34818056 |
Volume | 13 |
hasFullText | |
inHoldings | 1 |
isFullTextHit | |
isPrint | |
link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV3NTtwwELYWKiEuFf0vpZUP5RR5iRPn75ggEEJiD2WRuCHbmRQEZFfsLqp4qp77EH0mxrGzmy7bqu0liuLIij1fZsb2fDOEfOaCCy3LkKlQSSaCSjPp64qBCMokS7kOG1LYySA-OhPH59F5r_e9E7U0m6q-fljJK_kfqeIzlKthyf6DZOed4gO8R_niFSWM17-Sce7dmni6L4OcBZw1JJDGgcyHhVFQp9z3c5Poc3DIdvcPdou88OS3q4kJykIJwcTTNjWuN1Iuj-w9eOPZDQ7ABNO5wxuTe_Vy9NUoxatJ15lt9cLU2Lubdldx-bTe1Wt2DH5v7jqfzupreSdbTXNZywXXrLiT2kYNoSFYxDQem20cbQtt20hMVxrMbVvgJHDOLFu6D1bVZiJmhp3yiy4OO5iLLXfaqVaQ8j4JLDn5qd5vK1XaEeNI-yteR-mNbxssGPpx6tuU5n9uXcrG3TatkbUkNaVCBmZ3yFr-GL3Z2NEzHTHryedsko22i6WFTOPQDLfIc7cSobmF1QvSg_ol2Thx0ntFrnO6Cl20QdeexdYeIuvnj4IaVNEWVdShinZQReeoog5VtIuq1-Ts8GC4f8RcaQ6mwzCaMo2WIImysgJeJmWV-rLUIkyEzEByLSHiwBV6rgpUnKkkjgA9W6FwLcs1WgEVvCHr9aiGd4RCqqDC97JM4epBRxl2jeZbSiUjrQS8J2_tNF2Mbf6Vi3YCt3_b8oFsLjC3Q55V-MPDR_Qep-pTI7JHIiFyyg |
link.rule.ids | 780 |
linkProvider | National Library of Medicine |
openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=A+microRNA-21-mediated+SATB1%2FS100A9%2FNF-%CE%BAB+axis+promotes+chronic+obstructive+pulmonary+disease+pathogenesis&rft.jtitle=Science+translational+medicine&rft.au=Kim%2C+Richard+Y&rft.au=Sunkara%2C+Krishna+P&rft.au=Bracke%2C+Ken+R&rft.au=Jarnicki%2C+Andrew+G&rft.date=2021-11-24&rft.eissn=1946-6242&rft.volume=13&rft.issue=621&rft.spage=eaav7223&rft_id=info:doi/10.1126%2Fscitranslmed.aav7223&rft_id=info%3Apmid%2F34818056&rft_id=info%3Apmid%2F34818056&rft.externalDocID=34818056 |