Εξειδίκευση τύπου :	Άρθρο σε επιστημονικό περιοδικό
Τίτλος:	Association between DNA damage response, fibrosis and type I interferon signature in systemic sclerosis
Δημιουργός/Συγγραφέας:	Vlachogiannis, Nikolaos I Pappa, Maria Ntouros, Panagiotis A Nezos, Adrianos Mavragani, Clio P [EL] Σουλιώτης, Βασίλης Λ.[EN] Souliotis, Vassilis L. Sfikakis, Petros P
Ημερομηνία:	2020
Γλώσσα:	Αγγλικά
ISSN:	1664-3224
DOI:	10.3389/fimmu.2020.582401
Άλλο:	33123169
Περίληψη:	Increased endogenous DNA damage and type I interferon pathway activation have been implicated in systemic sclerosis (SSc) pathogenesis. Because experimental evidence suggests an interplay between DNA damage response/repair (DDR/R) and immune response, we hypothesized that deregulated DDR/R is associated with a type I interferon signature and/or fibrosis extent in SSc. DNA damage levels, oxidative stress, induction of abasic sites and the efficiency of DNA double-strand break repair (DSB/R) and nucleotide excision repair (NER) were assessed in peripheral blood mononuclear cells (PBMCs) derived from 37 SSc patients and 55 healthy controls; expression of DDR/R-associated genes and type I interferon-induced genes was also quantified. Endogenous DNA damage was significantly higher in untreated diffuse or limited SSc (Olive tail moment; 14.7 ± 7.0 and 9.5 ± 4.1, respectively) as well as in patients under cytotoxic treatment (15.0 ± 5.4) but not in very early onset SSc (5.6 ± 1.2) compared with controls (4.9 ± 2.6). Moreover, patients with pulmonary fibrosis had significantly higher DNA damage levels than those without (12.6 ± 5.8 vs. 8.8 ± 4.8, respectively). SSc patients displayed increased oxidative stress and abasic sites, defective DSB/R but not NER capacity, downregulation of genes involved in DSB/R (MRE11A, PRKDC) and base excision repair (PARP1, XRCC1), and upregulation of apoptosis-related genes (BAX, BBC3). Individual levels of DNA damage in SSc PBMCs correlated significantly with the corresponding mRNA expression of type I interferon-induced genes (IFIT1, IFI44 and MX1, r=0.419-0.490) as well as with corresponding skin involvement extent by modified Rodnan skin score (r=0.481). In conclusion, defective DDR/R may exert a fuel-on-fire effect on type I interferon pathway activation and contribute to tissue fibrosis in SSc.
Τίτλος πηγής δημοσίευσης:	Frontiers in immunology
Τόμος/Κεφάλαιο:	11
Σελίδες:	582401
Θεματική Κατηγορία:	[EL] Ιατρική (Γενικά)[EN] Medicine (General) [EL] Βιοχημεία[EN] Biochemistry [EL] Ανοσολογία[EN] Immunology [EL] Βιολογία (Γενικά)[EN] Biology (General)
Λέξεις-Κλειδιά:	DNA damage response and repair network Fibrosis Oxidative stress Systemic sclerosis (scleroderma) Type I interferon (IFN) Adult Aged Apoptosis Autoantibodies DNA Damage DNA Repair Female Humans Lung Male Middle Aged Scleroderma, Systemic
Κάτοχος πνευματικών δικαιωμάτων:	Copyright © 2020 Frontiers Media S.A. All rights reserved
Ηλεκτρονική διεύθυνση στον εκδότη (link):	https://www.frontiersin.org/articles/10.3389/fimmu.2020.582401/full
Ηλεκτρονική διεύθυνση περιοδικού (link) :	https://www.frontiersin.org/journals/immunology
Εμφανίζεται στις συλλογές:	Ινστιτούτο Χημικής Βιολογίας - Επιστημονικό έργο