3′mRNA sequencing reveals pro-regenerative properties of c5ar1 during resolution of murine acetaminophen-induced liver injury
- Murine acetaminophen-induced acute liver injury (ALI) serves as paradigmatic model for drug-induced hepatic injury and regeneration. As major cause of ALI, acetaminophen overdosing is a persistent therapeutic challenge with N-acetylcysteine clinically used to ameliorate parenchymal necrosis. To identify further treatment strategies that serve patients with poor N-acetylcysteine responses, hepatic 3′mRNA sequencing was performed in the initial resolution phase at 24 h/48 h after sublethal overdosing. This approach disclosed 45 genes upregulated (≥5-fold) within this time frame. Focusing on C5aR1, we observed in C5aR1-deficient mice disease aggravation during resolution of intoxication as evidenced by increased liver necrosis and serum alanine aminotransferase. Moreover, decreased hepatocyte compensatory proliferation and increased caspase-3 activation at the surroundings of necrotic cores were detectable in C5aR1-deficient mice. Using a non-hypothesis-driven approach, herein pro-regenerative/-resolving effects of C5aR1 were identified during late acetaminophen-induced ALI. Data concur with protection by the C5a/C5aR1-axis during hepatectomy and emphasize the complex role of inflammation during hepatic regeneration and repair.
Verfasserangaben: | Sina GontherGND, Malte BachmannGND, Itamar Goren, Arnaud HuardORCiDGND, Andreas WeigertORCiDGND, Jörg KöhlORCiDGND, Heiko MühlORCiDGND |
---|---|
URN: | urn:nbn:de:hebis:30:3-695328 |
DOI: | https://doi.org/10.1038/s41536-022-00206-x |
ISSN: | 2057-3995 |
Titel des übergeordneten Werkes (Englisch): | npj regenerative medicine |
Verlag: | Nature Publishing Group |
Verlagsort: | [London] |
Dokumentart: | Wissenschaftlicher Artikel |
Sprache: | Englisch |
Datum der Veröffentlichung (online): | 27.01.2022 |
Datum der Erstveröffentlichung: | 27.01.2022 |
Veröffentlichende Institution: | Universitätsbibliothek Johann Christian Senckenberg |
Datum der Freischaltung: | 13.07.2023 |
Freies Schlagwort / Tag: | Cell death and immune response; Hepatotoxicity |
Jahrgang: | 7 |
Ausgabe / Heft: | art. 10 |
Aufsatznummer: | 10 |
Seitenzahl: | 10 |
Erste Seite: | 1 |
Letzte Seite: | 10 |
Bemerkung: | Open Access funding enabled and organized by Projekt DEAL. |
Bemerkung: | The data sets generated and analyzed during this study are available from the corresponding author on reasonable request. Sequencing (MACE) data (Figs. 1d and 2) were deposited in NCBI’s Gene Expression Omnibus (GEO) under the accession number GSE169071. |
HeBIS-PPN: | 512609942 |
Institute: | Medizin |
DDC-Klassifikation: | 5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie |
6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit | |
Sammlungen: | Universitätspublikationen |
Lizenz (Deutsch): | Creative Commons - CC BY - Namensnennung 4.0 International |