Cytosolic nucleic acid sensors of the innate immune system promote liver regeneration after partial hepatectomy

Abstract Stimulation of cytosolic nucleic acid sensors of innate immunity by pathogen-derived nucleic acids is important for antimicrobial defence, but stimulation through self-derived nucleic acids may contribute to autoinflammation and cancer. DNA sensing in the cytosol requires the stimulator of...

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Autores principales:	Sarah Schulze, Christian Stöß, Miao Lu, Baocai Wang, Melanie Laschinger, Katja Steiger, Felicitas Altmayr, Helmut Friess, Daniel Hartmann, Bernhard Holzmann, Norbert Hüser
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e23109e2d28a4177896768238a57e86e
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spelling	oai:doaj.org-article:e23109e2d28a4177896768238a57e86e2021-12-02T15:08:13ZCytosolic nucleic acid sensors of the innate immune system promote liver regeneration after partial hepatectomy10.1038/s41598-018-29924-32045-2322https://doaj.org/article/e23109e2d28a4177896768238a57e86e2018-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-29924-3https://doaj.org/toc/2045-2322Abstract Stimulation of cytosolic nucleic acid sensors of innate immunity by pathogen-derived nucleic acids is important for antimicrobial defence, but stimulation through self-derived nucleic acids may contribute to autoinflammation and cancer. DNA sensing in the cytosol requires the stimulator of interferon genes (STING), while cytosolic RNA sensors use mitochondrial antiviral-signalling protein (MAVS). In a murine model of two-thirds hepatectomy, combined deficiency of MAVS and STING resulted in strongly impaired hepatocyte proliferation and delayed recovery of liver mass. Whereas lack of MAVS and STING did not influence upregulation of the G1-phase cyclins D1 and E1, it substantially reduced the hyperphosphorylation of retinoblastoma protein, attenuated the activation of cyclin-dependent kinase (CDK)-2, delayed upregulation of CDK1 and cyclins A2 and B1, and impaired S-phase entry of hepatocytes. Mechanistically, lack of cytosolic nucleic acid sensors strongly upregulated the anti-proliferative mediators TGF-β2 and activin A, which was associated with an increased expression of the cell cycle inhibitors p15 and p21. Partial hepatectomy was followed by the release of exosomes with abundant nucleic acid cargo, which may provide ligands for the MAVS and STING pathways. Together, these findings identify a previously unrecognised function of cytosolic nucleic acid sensors of innate immunity for promoting liver regeneration.Sarah SchulzeChristian StößMiao LuBaocai WangMelanie LaschingerKatja SteigerFelicitas AltmayrHelmut FriessDaniel HartmannBernhard HolzmannNorbert HüserNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-13 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sarah Schulze Christian Stöß Miao Lu Baocai Wang Melanie Laschinger Katja Steiger Felicitas Altmayr Helmut Friess Daniel Hartmann Bernhard Holzmann Norbert Hüser Cytosolic nucleic acid sensors of the innate immune system promote liver regeneration after partial hepatectomy
description	Abstract Stimulation of cytosolic nucleic acid sensors of innate immunity by pathogen-derived nucleic acids is important for antimicrobial defence, but stimulation through self-derived nucleic acids may contribute to autoinflammation and cancer. DNA sensing in the cytosol requires the stimulator of interferon genes (STING), while cytosolic RNA sensors use mitochondrial antiviral-signalling protein (MAVS). In a murine model of two-thirds hepatectomy, combined deficiency of MAVS and STING resulted in strongly impaired hepatocyte proliferation and delayed recovery of liver mass. Whereas lack of MAVS and STING did not influence upregulation of the G1-phase cyclins D1 and E1, it substantially reduced the hyperphosphorylation of retinoblastoma protein, attenuated the activation of cyclin-dependent kinase (CDK)-2, delayed upregulation of CDK1 and cyclins A2 and B1, and impaired S-phase entry of hepatocytes. Mechanistically, lack of cytosolic nucleic acid sensors strongly upregulated the anti-proliferative mediators TGF-β2 and activin A, which was associated with an increased expression of the cell cycle inhibitors p15 and p21. Partial hepatectomy was followed by the release of exosomes with abundant nucleic acid cargo, which may provide ligands for the MAVS and STING pathways. Together, these findings identify a previously unrecognised function of cytosolic nucleic acid sensors of innate immunity for promoting liver regeneration.
format	article
author	Sarah Schulze Christian Stöß Miao Lu Baocai Wang Melanie Laschinger Katja Steiger Felicitas Altmayr Helmut Friess Daniel Hartmann Bernhard Holzmann Norbert Hüser
author_facet	Sarah Schulze Christian Stöß Miao Lu Baocai Wang Melanie Laschinger Katja Steiger Felicitas Altmayr Helmut Friess Daniel Hartmann Bernhard Holzmann Norbert Hüser
author_sort	Sarah Schulze
title	Cytosolic nucleic acid sensors of the innate immune system promote liver regeneration after partial hepatectomy
title_short	Cytosolic nucleic acid sensors of the innate immune system promote liver regeneration after partial hepatectomy
title_full	Cytosolic nucleic acid sensors of the innate immune system promote liver regeneration after partial hepatectomy
title_fullStr	Cytosolic nucleic acid sensors of the innate immune system promote liver regeneration after partial hepatectomy
title_full_unstemmed	Cytosolic nucleic acid sensors of the innate immune system promote liver regeneration after partial hepatectomy
title_sort	cytosolic nucleic acid sensors of the innate immune system promote liver regeneration after partial hepatectomy
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/e23109e2d28a4177896768238a57e86e
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Cytosolic nucleic acid sensors of the innate immune system promote liver regeneration after partial hepatectomy

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