Journal Article

DZNE-2022-00448

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png The arginine methyltransferase PRMT7 promotes extravasation of monocytes resulting in tissue injury in COPD.

Günes Günsel, 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. C. ; Edelmann, S. L. ; Kohlhepp, M. S. ; Guillot, A. ; Bassler, K. ; Van Eeckhoutte, H. P. ; Kayalar, Ö. ; Konyalilar, N. ; Kanashova, T. ; Rodius, S. ; Ballester-López, C. ; Genes Robles, C. M. ; Smirnova, N. ; Rehberg, M. ; Agarwal, C. ; Krikki, I. ; Piavaux, B. ; Verleden, S. E. ; Vanaudenaerde, B. ; Königshoff, M. ; Dittmar, G. ; Bracke, K. R. ; Schultze, J. L.DZNE* ; Watz, H. ; Eickelberg, O. ; Stoeger, T. ; Burgstaller, G. ; Tacke, F. ; Heissmeyer, V. ; Rinkevich, Y. ; Bayram, H. ; Schiller, H. B. ; Conrad, M.Extern* ; Schneider, R. ; Yildirim, A. Ö.

2022
Nature Publishing Group UK [London]

This record in other databases:    

Please use a persistent id in citations: doi:10.1038/s41467-022-28809-4

Abstract: 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.

Keyword(s): Animals (MeSH) ; Arginine: metabolism (MeSH) ; Histones: metabolism (MeSH) ; Humans (MeSH) ; Intracellular Signaling Peptides and Proteins (MeSH) ; Mice (MeSH) ; Monocytes: metabolism (MeSH) ; Protein-Arginine N-Methyltransferases: metabolism (MeSH) ; Pulmonary Disease, Chronic Obstructive: genetics (MeSH) ; Histones ; Intracellular Signaling Peptides and Proteins ; Arginine ; PRMT2 protein, human ; PRMT7 protein, human ; PRMT7 protein, mouse ; Protein-Arginine N-Methyltransferases

---

Contributing Institute(s):

1. Platform for Single Cell Genomics and Epigenomics (PRECISE)
2. Clinical Single Cell Omics (CSCO) / Systems Medicine (AG Schultze)

Research Program(s):

1. 354 - Disease Prevention and Healthy Aging (POF4-354) (POF4-354)

Experiment(s):

1. Platform for Single Cell Genomics and Epigenomics at DZNE University of Bonn

Appears in the scientific report 2022

---

Database coverage:
; ; ; ; Article Processing Charges ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Agriculture, Biology and Environmental Sciences ; Current Contents - Life Sciences ; Current Contents - Physical, Chemical and Earth Sciences ; DOAJ Seal ; Essential Science Indicators ; Fees ; IF >= 15 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection ; Zoological Record

---