The arginine methyltransferase PRMT7 promotes extravasation of monocytes resulting in tissue injury in COPD.

Autor: Günes Günsel G; Institute of Lung Health and Immunity (LHI), Comprehensive Pneumology Center (CPC), Helmholtz Munich, Member of the German Center for Lung Research (DZL), 85764, Munich, Germany., Conlon TM; Institute of Lung Health and Immunity (LHI), Comprehensive Pneumology Center (CPC), Helmholtz Munich, Member of the German Center for Lung Research (DZL), 85764, Munich, Germany., Jeridi A; Institute of Lung Health and Immunity (LHI), Comprehensive Pneumology Center (CPC), Helmholtz Munich, Member of the German Center for Lung Research (DZL), 85764, Munich, Germany., Kim R; Institute of Functional Epigenetics, Helmholtz Munich, 85764, Munich, Germany., Ertüz Z; Institute of Lung Health and Immunity (LHI), Comprehensive Pneumology Center (CPC), Helmholtz Munich, Member of the German Center for Lung Research (DZL), 85764, Munich, Germany., Lang NJ; Institute of Lung Health and Immunity (LHI), Comprehensive Pneumology Center (CPC), Helmholtz Munich, Member of the German Center for Lung Research (DZL), 85764, Munich, Germany., Ansari M; Institute of Lung Health and Immunity (LHI), Comprehensive Pneumology Center (CPC), Helmholtz Munich, Member of the German Center for Lung Research (DZL), 85764, Munich, Germany.; Institute of Computational Biology, Helmholtz Munich, 85764, Munich, Germany., Novikova M; Institute of Metabolism and Cell Death, Helmholtz Munich, 85764, Munich, Germany.; Pirogov Russian National Research Medical University, Laboratory of Experimental Oncology, Ostrovityanova 1, Moscow, 117997, Russia.; Federal Center of Brain Research and Neurotechnologies, Federal Medical Biological Agency, Ostrovityanova1 bldg 10, 117997, Moscow, Russia., Jiang D; Institute of Lung Health and Immunity (LHI), Comprehensive Pneumology Center (CPC), Helmholtz Munich, Member of the German Center for Lung Research (DZL), 85764, Munich, Germany., Strunz M; Institute of Lung Health and Immunity (LHI), Comprehensive Pneumology Center (CPC), Helmholtz Munich, Member of the German Center for Lung Research (DZL), 85764, Munich, Germany., Gaianova M; Institute of Lung Health and Immunity (LHI), Comprehensive Pneumology Center (CPC), Helmholtz Munich, Member of the German Center for Lung Research (DZL), 85764, Munich, Germany., Hollauer C; Institute of Lung Health and Immunity (LHI), Comprehensive Pneumology Center (CPC), Helmholtz Munich, Member of the German Center for Lung Research (DZL), 85764, Munich, Germany., Gabriel C; Institute of Lung Health and Immunity (LHI), Comprehensive Pneumology Center (CPC), Helmholtz Munich, Member of the German Center for Lung Research (DZL), 85764, Munich, Germany., Angelidis I; Institute of Lung Health and Immunity (LHI), Comprehensive Pneumology Center (CPC), Helmholtz Munich, Member of the German Center for Lung Research (DZL), 85764, Munich, Germany., Doll S; Institute of Computational Biology, Helmholtz Munich, 85764, Munich, Germany., Pestoni JC; Institute of Lung Health and Immunity (LHI), Comprehensive Pneumology Center (CPC), Helmholtz Munich, Member of the German Center for Lung Research (DZL), 85764, Munich, Germany., Edelmann SL; Research Unit Molecular Immune Regulation, Helmholtz Munich, 81377, Munich, Germany., Kohlhepp MS; Department of Hepatology & Gastroenterology, Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum (CVK) and Campus Charité Mitte (CCM), 13353, Berlin, Germany., Guillot A; Department of Hepatology & Gastroenterology, Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum (CVK) and Campus Charité Mitte (CCM), 13353, Berlin, Germany., Bassler K; Department for Genomics & Immunoregulation, LIMES-Institute, University of Bonn, 53115, Bonn, Germany.; aimed analytics, 53121, Bonn, Germany., Van Eeckhoutte HP; Laboratory for Translational Research in Obstructive Pulmonary Diseases, Department of Respiratory Medicine, Ghent University, University Hospital Ghent, 9000, Ghent, Belgium., Kayalar Ö; Koç University Research Center for Translational Medicine (KUTTAM), 34010, Istanbul, Turkey., Konyalilar N; Koç University Research Center for Translational Medicine (KUTTAM), 34010, Istanbul, Turkey., Kanashova T; Max-Delbrück Center for Molecular Medicine, 13125, Berlin, Germany., Rodius S; Proteomics of cellular signalling, Luxembourg Institute of Health, 1272, Strassen, Luxembourg., Ballester-López C; Institute of Lung Health and Immunity (LHI), Comprehensive Pneumology Center (CPC), Helmholtz Munich, Member of the German Center for Lung Research (DZL), 85764, Munich, Germany., Genes Robles CM; Institute of Functional Epigenetics, Helmholtz Munich, 85764, Munich, Germany., Smirnova N; Institute of Lung Health and Immunity (LHI), Comprehensive Pneumology Center (CPC), Helmholtz Munich, Member of the German Center for Lung Research (DZL), 85764, Munich, Germany.; Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado, Denver, CO, 80045, USA., Rehberg M; Institute of Lung Health and Immunity (LHI), Comprehensive Pneumology Center (CPC), Helmholtz Munich, Member of the German Center for Lung Research (DZL), 85764, Munich, Germany., Agarwal C; Institute of Lung Health and Immunity (LHI), Comprehensive Pneumology Center (CPC), Helmholtz Munich, Member of the German Center for Lung Research (DZL), 85764, Munich, Germany., Krikki I; Institute of Lung Health and Immunity (LHI), Comprehensive Pneumology Center (CPC), Helmholtz Munich, Member of the German Center for Lung Research (DZL), 85764, Munich, Germany., Piavaux B; Czech Centre for Phenogenomics, Institute of Molecular Genetics of the Czech Academy of Sciences, 25242, Vestec, Czech Republic., Verleden SE; Division of Pneumology, KU Leuven, 3000, Leuven, Belgium.; Antwerp Surgical Training, Anatomy and Research Centre, University of Antwerp, 2650, Edegem, Belgium., Vanaudenaerde B; Division of Pneumology, KU Leuven, 3000, Leuven, Belgium., Königshoff M; Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, 15261, USA., Dittmar G; Proteomics of cellular signalling, Luxembourg Institute of Health, 1272, Strassen, Luxembourg.; Faculty of Science, Technology and Medicine, University of Luxembourg, L-4365, Esch-sur-Alzette, Luxembourg., Bracke KR; Laboratory for Translational Research in Obstructive Pulmonary Diseases, Department of Respiratory Medicine, Ghent University, University Hospital Ghent, 9000, Ghent, Belgium., Schultze JL; Department for Genomics & Immunoregulation, LIMES-Institute, University of Bonn, 53115, Bonn, Germany.; Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) e.V., PRECISE Platform for Single Cell Genomics and Epigenomics at DZNE and the University of Bonn, 53115, Bonn, Germany., Watz H; Pulmonary Research Institute at LungenClinic Grosshansdorf, Airway Research Center North (ARCN), German Center for Lung Research (DZL), 22927, Grosshansdorf, Germany., Eickelberg O; Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, 15261, USA., Stoeger T; Institute of Lung Health and Immunity (LHI), Comprehensive Pneumology Center (CPC), Helmholtz Munich, Member of the German Center for Lung Research (DZL), 85764, Munich, Germany., Burgstaller G; Institute of Lung Health and Immunity (LHI), Comprehensive Pneumology Center (CPC), Helmholtz Munich, Member of the German Center for Lung Research (DZL), 85764, Munich, Germany., Tacke F; Department of Hepatology & Gastroenterology, Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum (CVK) and Campus Charité Mitte (CCM), 13353, Berlin, Germany., Heissmeyer V; Research Unit Molecular Immune Regulation, Helmholtz Munich, 81377, Munich, Germany.; Institute for Immunology, Biomedical Center, Faculty of Medicine, Ludwig-Maximilians-Universität in Munich, 82152, Planegg-Martinsried, Germany., Rinkevich Y; Institute of Lung Health and Immunity (LHI), Comprehensive Pneumology Center (CPC), Helmholtz Munich, Member of the German Center for Lung Research (DZL), 85764, Munich, Germany., Bayram H; Koç University Research Center for Translational Medicine (KUTTAM), 34010, Istanbul, Turkey., Schiller HB; Institute of Lung Health and Immunity (LHI), Comprehensive Pneumology Center (CPC), Helmholtz Munich, Member of the German Center for Lung Research (DZL), 85764, Munich, Germany., Conrad M; Institute of Metabolism and Cell Death, Helmholtz Munich, 85764, Munich, Germany.; Pirogov Russian National Research Medical University, Laboratory of Experimental Oncology, Ostrovityanova 1, Moscow, 117997, Russia., Schneider R; Institute of Functional Epigenetics, Helmholtz Munich, 85764, Munich, Germany., Yildirim AÖ; Institute of Lung Health and Immunity (LHI), Comprehensive Pneumology Center (CPC), Helmholtz Munich, Member of the German Center for Lung Research (DZL), 85764, Munich, Germany. oender.yildirim@helmholtz-muenchen.de.; Koç University Research Center for Translational Medicine (KUTTAM), 34010, Istanbul, Turkey. oender.yildirim@helmholtz-muenchen.de.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2022 Mar 14; Vol. 13 (1), pp. 1303. Date of Electronic Publication: 2022 Mar 14.
DOI: 10.1038/s41467-022-28809-4
Abstrakt: Extravasation of monocytes into tissue and to the site of injury is a fundamental immunological process, which requires rapid responses via post translational modifications (PTM) of proteins. Protein arginine methyltransferase 7 (PRMT7) is an epigenetic factor that has the capacity to mono-methylate histones on arginine residues. Here we show that in chronic obstructive pulmonary disease (COPD) patients, PRMT7 expression is elevated in the lung tissue and localized to the macrophages. In mouse models of COPD, lung fibrosis and skin injury, reduced expression of PRMT7 associates with decreased recruitment of monocytes to the site of injury and hence less severe symptoms. Mechanistically, activation of NF-κB/RelA in monocytes induces PRMT7 transcription and consequential mono-methylation of histones at the regulatory elements of RAP1A, which leads to increased transcription of this gene that is responsible for adhesion and migration of monocytes. Persistent monocyte-derived macrophage accumulation leads to ALOX5 over-expression and accumulation of its metabolite LTB4, which triggers expression of ACSL4 a ferroptosis promoting gene in lung epithelial cells. Conclusively, inhibition of arginine mono-methylation might offer targeted intervention in monocyte-driven inflammatory conditions that lead to extensive tissue damage if left untreated.
(© 2022. The Author(s).)
Databáze: MEDLINE
Externí odkaz: