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| Verfasst von: | Hammad, Seddik [VerfasserIn]  |
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| | Ogris, Christoph [VerfasserIn] |
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| | Othman, Amnah [VerfasserIn] |
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| | Erdoesi, Pia [VerfasserIn] |
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| | Schmidt-Heck, Wolfgang [VerfasserIn] |
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| | Biermayer, Ina [VerfasserIn] |
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| | Helm, Barbara [VerfasserIn] |
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| | Gao, Yan [VerfasserIn] |
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| | Piorońska, Weronika [VerfasserIn] |
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| | Holland, Christian H. [VerfasserIn] |
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| | D'Alessandro, Lorenza [VerfasserIn] |
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| | Torre, Carolina de la [VerfasserIn] |
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| | Sticht, Carsten [VerfasserIn] |
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| | Al Aoua, Sherin [VerfasserIn] |
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| | Theis, Fabian J. [VerfasserIn] |
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| | Bantel, Heike [VerfasserIn] |
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| | Ebert, Matthias [VerfasserIn] |
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| | Klingmüller, Ursula [VerfasserIn] |
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| | Hengstler, Jan G. [VerfasserIn] |
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| | Dooley, Steven [VerfasserIn] |
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| | Mueller, Nikola S. [VerfasserIn] |
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| Titel: | Tolerance of repeated toxic injuries of murine livers is associated with steatosis and inflammation |
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| Verf.angabe: | Seddik Hammad, Christoph Ogris, Amnah Othman, Pia Erdoesi, Wolfgang Schmidt-Heck, Ina Biermayer, Barbara Helm, Yan Gao, Weronika Piorońska, Christian H. Holland, Lorenza A. D’Alessandro, Carolina de la Torre, Carsten Sticht, Sherin Al Aoua, Fabian J. Theis, Heike Bantel, Matthias P. Ebert, Ursula Klingmüller, Jan G. Hengstler, Steven Dooley and Nikola S. Mueller |
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| Jahr: | 2023 |
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| Umfang: | 13 S. |
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| Illustrationen: | Illustrationen |
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| Fussnoten: | Veröffentlicht: 12. Juli 2023 ; Gesehen am 29.08.2023 |
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| Titel Quelle: | Enthalten in: Cell death & disease |
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| Ort Quelle: | London [u.a.] : Nature Publishing Group, 2010 |
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| Jahr Quelle: | 2023 |
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| Band/Heft Quelle: | 14(2023), 7, Artikel-ID 414, Seite 1-13 |
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| ISSN Quelle: | 2041-4889 |
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| Abstract: | The human liver has a remarkable capacity to regenerate and thus compensate over decades for fibrosis caused by toxic chemicals, drugs, alcohol, or malnutrition. To date, no protective mechanisms have been identified that help the liver tolerate these repeated injuries. In this study, we revealed dysregulation of lipid metabolism and mild inflammation as protective mechanisms by studying longitudinal multi-omic measurements of liver fibrosis induced by repeated CCl4 injections in mice (n = 45). Based on comprehensive proteomics, transcriptomics, blood- and tissue-level profiling, we uncovered three phases of early disease development—initiation, progression, and tolerance. Using novel multi-omic network analysis, we identified multi-level mechanisms that are significantly dysregulated in the injury-tolerant response. Public data analysis shows that these profiles are altered in human liver diseases, including fibrosis and early cirrhosis stages. Our findings mark the beginning of the tolerance phase as the critical switching point in liver response to repetitive toxic doses. After fostering extracellular matrix accumulation as an acute response, we observe a deposition of tiny lipid droplets in hepatocytes only in the Tolerant phase. Our comprehensive study shows that lipid metabolism and mild inflammation may serve as biomarkers and are putative functional requirements to resist further disease progression. |
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| DOI: | doi:10.1038/s41419-023-05855-4 |
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| URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
kostenfrei: Volltext: https://doi.org/10.1038/s41419-023-05855-4 |
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| | kostenfrei: Volltext: https://www.nature.com/articles/s41419-023-05855-4 |
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| | DOI: https://doi.org/10.1038/s41419-023-05855-4 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| Sach-SW: | Experimental models of disease |
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| | Liver fibrosis |
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| | Prognostic markers |
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| | Transcriptomics |
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| K10plus-PPN: | 1858163684 |
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| Verknüpfungen: | → Zeitschrift |
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Tolerance of repeated toxic injuries of murine livers is associated with steatosis and inflammation / Hammad, Seddik [VerfasserIn]; 2023 (Online-Ressource)
