ID | 112459 |
Author |
Iwata, Hiroshi
Harvard Medical School
Goettsch, Claudia
Harvard Medical School
Sharma, Amitabh
Harvard Medical School|Northeastern University
Ricchiuto, Piero
Harvard Medical School
Goh, Wilson Wen Bin
Harvard Medical School
Halu, Arda
Harvard Medical School
Yamada, Iwao
Harvard Medical School
Yoshida, Hideo
Harvard Medical School
Tokushima University Educator and Researcher Directory
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Hara, Takuya
Harvard Medical School
Wei, Mei
Vanderbilt University
Inoue, Noriyuki
Harvard Medical School
Mojcher, Alexander
Harvard Medical School
Mattson, Peter C.
Harvard Medical School
Barabási, Albert-László
Harvard Medical School|Northeastern University
Boothby, Mark
Vanderbilt University
Aikawa, Elena
Harvard Medical School
Singh, Sasha A.
Harvard Medical School
Aikawa, Masanori
Harvard Medical School
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Content Type |
Journal Article
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Description | Despite the global impact of macrophage activation in vascular disease, the underlying mechanisms remain obscure. Here we show, with global proteomic analysis of macrophage cell lines treated with either IFNγ or IL-4, that PARP9 and PARP14 regulate macrophage activation. In primary macrophages, PARP9 and PARP14 have opposing roles in macrophage activation. PARP14 silencing induces pro-inflammatory genes and STAT1 phosphorylation in M(IFNγ) cells, whereas it suppresses anti-inflammatory gene expression and STAT6 phosphorylation in M(IL-4) cells. PARP9 silencing suppresses pro-inflammatory genes and STAT1 phosphorylation in M(IFNγ) cells. PARP14 induces ADP-ribosylation of STAT1, which is suppressed by PARP9. Mutations at these ADP-ribosylation sites lead to increased phosphorylation. Network analysis links PARP9–PARP14 with human coronary artery disease. PARP14 deficiency in haematopoietic cells accelerates the development and inflammatory burden of acute and chronic arterial lesions in mice. These findings suggest that PARP9 and PARP14 cross-regulate macrophage activation.
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Journal Title |
Nature Communications
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ISSN | 20411723
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NCID | AA12645905
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Publisher | Springer Nature
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Volume | 7
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Start Page | 12849
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Published Date | 2016-10-31
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Remark | Supplementary Information : ncomms_7_12849_s1.pdf
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Rights | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
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DOI (Published Version) | |
URL ( Publisher's Version ) | |
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language |
eng
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TextVersion |
Publisher
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departments |
Oral Sciences
Medical Sciences
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