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| Verfasst von: | Sugimoto, Atsushi [VerfasserIn]  |
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| | Saito, Yoshinobu [VerfasserIn] |
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| | Wang, Guanxiong [VerfasserIn] |
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| | Sun, Qiuyan [VerfasserIn] |
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| | Yin, Chuan [VerfasserIn] |
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| | Lee, Ki Hong [VerfasserIn] |
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| | Geng, Yana [VerfasserIn] |
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| | Rajbhandari, Presha [VerfasserIn] |
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| | Hernandez, Celine [VerfasserIn] |
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| | Steffani, Marcella [VerfasserIn] |
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| | Qie, Jingran [VerfasserIn] |
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| | Savage, Thomas [VerfasserIn] |
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| | Goyal, Dhruv M. [VerfasserIn] |
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| | Ray, Kevin C. [VerfasserIn] |
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| | Neelakantan, Taruna V. [VerfasserIn] |
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| | Yin, Deqi [VerfasserIn] |
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| | Melms, Johannes [VerfasserIn] |
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| | Lehrich, Brandon M. [VerfasserIn] |
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| | Yasaka, Tyler M. [VerfasserIn] |
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| | Liu, Silvia [VerfasserIn] |
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| | Oertel, Michael [VerfasserIn] |
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| | Lan, Tian [VerfasserIn] |
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| | Guillot, Adrien [VerfasserIn] |
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| | Peiseler, Moritz [VerfasserIn] |
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| | Filliol, Aveline [VerfasserIn] |
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| | Kanzaki, Hiroaki [VerfasserIn] |
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| | Fujiwara, Naoto [VerfasserIn] |
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| | Ravi, Samhita [VerfasserIn] |
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| | Izar, Benjamin [VerfasserIn] |
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| | Brosch, Mario [VerfasserIn] |
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| | Hampe, Jochen [VerfasserIn] |
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| | Remotti, Helen [VerfasserIn] |
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| | Argemi, Josepmaria [VerfasserIn] |
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| | Sun, Zhaoli [VerfasserIn] |
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| | Kendall, Timothy J. [VerfasserIn] |
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| | Hoshida, Yujin [VerfasserIn] |
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| | Tacke, Frank [VerfasserIn] |
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| | Fallowfield, Jonathan A. [VerfasserIn] |
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| | Blockley-Powell, Storm K. [VerfasserIn] |
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| | Haeusler, Rebecca A. [VerfasserIn] |
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| | Steinman, Jonathan B. [VerfasserIn] |
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| | Pajvani, Utpal B. [VerfasserIn] |
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| | Monga, Satdarshan P. [VerfasserIn] |
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| | Bataller, Ramon [VerfasserIn] |
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| | Masoodi, Mojgan [VerfasserIn] |
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| | Arpaia, Nicholas [VerfasserIn] |
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| | Lee, Youngmin A. [VerfasserIn] |
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| | Stockwell, Brent R. [VerfasserIn] |
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| | Augustin, Hellmut [VerfasserIn] |
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| | Schwabe, Robert F. [VerfasserIn] |
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| Titel: | Hepatic stellate cells control liver zonation, size and functions via R-spondin 3 |
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| Verf.angabe: | Atsushi Sugimoto, Yoshinobu Saito, Guanxiong Wang, Qiuyan Sun, Chuan Yin, Ki Hong Lee, Yana Geng, Presha Rajbhandari, Celine Hernandez, Marcella Steffani, Jingran Qie, Thomas Savage, Dhruv M. Goyal, Kevin C. Ray, Taruna V. Neelakantan, Deqi Yin, Johannes Melms, Brandon M. Lehrich, Tyler M. Yasaka, Silvia Liu, Michael Oertel, Tian Lan, Adrien Guillot, Moritz Peiseler, Aveline Filliol, Hiroaki Kanzaki, Naoto Fujiwara, Samhita Ravi, Benjamin Izar, Mario Brosch, Jochen Hampe, Helen Remotti, Josepmaria Argemi, Zhaoli Sun, Timothy J. Kendall, Yujin Hoshida, Frank Tacke, Jonathan A. Fallowfield, Storm K. Blockley-Powell, Rebecca A. Haeusler, Jonathan B. Steinman, Utpal B. Pajvani, Satdarshan P. Monga, Ramon Bataller, Mojgan Masoodi, Nicholas Arpaia, Youngmin A. Lee, Brent R. Stockwell, Hellmut G. Augustin & Robert F. Schwabe |
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| E-Jahr: | 2025 |
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| Jahr: | 17 April 2025 |
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| Umfang: | 34 S. |
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| Illustrationen: | Illustrationen |
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| Fussnoten: | Online veröffentlicht: 12. März 2025 ; Gesehen am 18.06.2025 |
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| Titel Quelle: | Enthalten in: Nature |
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| Ort Quelle: | London [u.a.] : Nature Publ. Group, 1869 |
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| Jahr Quelle: | 2025 |
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| Band/Heft Quelle: | 640(2025), 8059, Seite 752-761 |
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| ISSN Quelle: | 1476-4687 |
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| Abstract: | Hepatic stellate cells (HSCs) have a central pathogenetic role in the development of liver fibrosis. However, their fibrosis-independent and homeostatic functions remain poorly understood1-5. Here we demonstrate that genetic depletion of HSCs changes WNT activity and zonation of hepatocytes, leading to marked alterations in liver regeneration, cytochrome P450 metabolism and injury. We identify R-spondin 3 (RSPO3), an HSC-enriched modulator of WNT signalling, as responsible for these hepatocyte-regulatory effects of HSCs. HSC-selective deletion of Rspo3 phenocopies the effects of HSC depletion on hepatocyte gene expression, zonation, liver size, regeneration and cytochrome P450-mediated detoxification, and exacerbates alcohol-associated and metabolic dysfunction-associated steatotic liver disease. RSPO3 expression decreases with HSC activation and is inversely associated with outcomes in patients with alcohol-associated and metabolic dysfunction-associated steatotic liver disease. These protective and hepatocyte-regulating functions of HSCs via RSPO3 resemble the R-spondin-expressing stromal niche in other organs and should be integrated into current therapeutic concepts. |
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| DOI: | doi:10.1038/s41586-025-08677-w |
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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/s41586-025-08677-w |
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| | kostenfrei: Volltext: https://www.nature.com/articles/s41586-025-08677-w |
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| | DOI: https://doi.org/10.1038/s41586-025-08677-w |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| Sach-SW: | Cell signalling |
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| | Mechanisms of disease |
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| K10plus-PPN: | 192852866X |
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| Verknüpfungen: | → Zeitung |
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Hepatic stellate cells control liver zonation, size and functions via R-spondin 3 / Sugimoto, Atsushi [VerfasserIn]; 17 April 2025 (Online-Ressource)
