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Tytuł pozycji:

Toll-like receptor 9 signaling after myocardial infarction: Role of p66ShcA adaptor protein.

Tytuł:
Toll-like receptor 9 signaling after myocardial infarction: Role of p66ShcA adaptor protein.
Autorzy:
Baysa A; Department of Molecular Medicine, Institute of Basic Medical Science University of Oslo, Norway.
Maghazachi AA; Department of Molecular Medicine, Institute of Basic Medical Science University of Oslo, Norway.
Sand KL; Department of Molecular Medicine, Institute of Basic Medical Science University of Oslo, Norway.
Campesan M; Department of Biomedical Sciences, University of Padua, Padua, Italy.
Zaglia T; Venetian Institute of Molecular Medicine, Padova, Italy.
Mongillo M; Department of Biomedical Sciences, University of Padua, Padua, Italy; CNR Institute of Neuroscience, University of Padua, Padua, Italy; Venetian Institute of Molecular Medicine, Padova, Italy.
Giorgio M; Department of Experimental Oncology, European Institute of Oncology, Milan, Italy.
Di Lisa F; Department of Biomedical Sciences, University of Padua, Padua, Italy; CNR Institute of Neuroscience, University of Padua, Padua, Italy.
Gullestad L; Department of Cardiology, Oslo University Hospital, Oslo, Norway; KG Jebsen Center for Cardiac Research, University of Oslo, Norway.
Mariero LH; Department of Molecular Medicine, Institute of Basic Medical Science University of Oslo, Norway.
Vaage J; Department of Molecular Medicine, Institute of Basic Medical Science University of Oslo, Norway; Department of Research and Development, Division of Critical Care and Emergencies, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Valen G; Department of Molecular Medicine, Institute of Basic Medical Science University of Oslo, Norway.
Stensløkken KO; Department of Molecular Medicine, Institute of Basic Medical Science University of Oslo, Norway. Electronic address: .
Źródło:
Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2023 Feb 12; Vol. 644, pp. 70-78. Date of Electronic Publication: 2022 Dec 30.
Typ publikacji:
Journal Article; Research Support, Non-U.S. Gov't
Język:
English
Imprint Name(s):
Publication: <2002- >: San Diego, CA : Elsevier
Original Publication: New York, Academic Press.
MeSH Terms:
Heart Failure*
Myocardial Infarction*/metabolism
Myocardial Ischemia*
Animals ; Mice ; Adaptor Proteins, Signal Transducing/metabolism ; Inflammation ; Mice, Inbred C57BL ; Mice, Knockout ; NF-kappa B/metabolism ; Src Homology 2 Domain-Containing, Transforming Protein 1/metabolism ; Toll-Like Receptor 9/metabolism
Substance Nomenclature:
0 (Adaptor Proteins, Signal Transducing)
0 (NF-kappa B)
0 (Src Homology 2 Domain-Containing, Transforming Protein 1)
0 (Toll-Like Receptor 9)
0 (Shc1 protein, mouse)
Entry Date(s):
Date Created: 20230112 Date Completed: 20230208 Latest Revision: 20230301
Update Code:
20240105
DOI:
10.1016/j.bbrc.2022.12.085
PMID:
36634584
Czasopismo naukowe
During myocardial infarction, cellular debris is released, causing a sterile inflammation via pattern recognition receptors. These reactions amplify damage and promotes secondary heart failure. The pattern recognition receptor, Toll-like receptor 9 (TLR9) detects immunogenic fragments of endogenous DNA, inducing inflammation by NFκB. The p66ShcA adaptor protein plays an important role in both ischemic myocardial damage and immune responses. We hypothesized that p66ShcA adaptor protein promotes DNA-sensing signaling via the TLR9 pathway after myocardial infarction. TLR9 protein expression increased in cardiac tissue from patients with end-stage heart failure due to ischemic heart disease. Myocardial ischemia in mice in vivo induced gene expression of key TLR9 pathway proteins (MyD88 and Unc93b1). In this model, a functional link between TLR9 and p66ShcA was revealed as; (i) ischemia-induced upregulation of TLR9 protein was abrogated in myocardium of p66ShcA knockout mice; (ii) when p66ShcA was overexpressed in NFkB reporter cells stably expressing TLR9, NFkB-activation increased during stimulation with the TLR9 agonist CpG B; (iii) in cardiac fibroblasts, p66ShcA overexpression caused TLR9 upregulation. Co-immunoprecipitation showed that ShcA proteins and TLR9 may be found in the same protein complex, which was dissipated upon TLR9 stimulation in vivo. A proximity assay confirmed the co-localization of TLR9 and ShcA proteins. The systemic immune response after myocardial ischemia was dampened in p66ShcA knockout mice as interleukin-4, -17 and -22 expression in mononuclear cells isolated from spleens was reduced. In conclusion, p66ShcA adaptor may be an interaction partner and a regulator of the TLR9 pathway post-infarction.
Competing Interests: Declaration of competing interest No conflict of interest.
(Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

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