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Günsel, G.G. ; Conlon, T.M. ; Jeridi, A. ; Kim, R. ; Ertüz, Z. ; Lang, N.J. ; Ansari, M. ; Novikova, M. ; Jiang, D. ; Strunz, M. ; Gaianova, M. ; Hollauer, C. ; Gabriel, C. ; Angelidis, I. ; Doll, S. ; Pestoni, J. ; Edelmann, S.L. ; Kohlhepp, M.S.* ; Guillot, A.* ; Bassler, K.* ; Van Eeckhoutte, H.P.* ; Kayalar, Ö.* ; Konyalilar, N.* ; Kanashova, T.* ; Rodius, S.* ; Ballester-Lopez, C. ; Genes Robles, C.M. ; Smirnova, N.F. ; Rehberg, M. ; Agarwal, C. ; Krikki, I. ; Piavaux, B.* ; Verleden, S.E.* ; Vanaudenaerde, B.* ; Königshoff, M.* ; Dittmar, G.* ; Bracke, K.R.* ; Schultze, J.L.* ; Watz, H.* ; Eickelberg, O.* ; Stöger, T. ; Burgstaller, G. ; Tacke, F.* ; Heissmeyer, V. ; Rinkevich, Y. ; Bayram, H.* ; Schiller, H. B. ; Conrad, M. ; Schneider, R. ; Yildirim, A.Ö.

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

Nat. Commun. 13:1303 (2022)
Postprint Research data DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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.
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Publication type Article: Journal article
Document type Scientific Article
Language english
Publication Year 2022
HGF-reported in Year 2022
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Quellenangaben Volume: 13, Issue: 1, Pages: , Article Number: 1303 Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Reviewing status Peer reviewed
POF-Topic(s) 30202 - Environmental Health
30203 - Molecular Targets and Therapies
80000 - German Center for Lung Research
30205 - Bioengineering and Digital Health
Research field(s) Lung Research
Helmholtz Diabetes Center
Genetics and Epidemiology
Enabling and Novel Technologies
Immune Response and Infection
PSP Element(s) G-505000-007
G-502800-001
G-501800-810
G-506900-001
G-509400-001
G-503800-001
G-501800-820
G-501712-001
G-501600-001
G-505000-001
G-501600-014
Grants EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)
Deutsche Forschungsgemeinschaft (German Research Foundation)
Scopus ID 85126201736
PubMed ID 35288557
Erfassungsdatum 2022-05-05