Lymphotoxin-β-receptor (LTβR) signaling on hepatocytes is required for liver regeneration after partial hepatectomy
| Autor: | Nicole Küpper, Patrick Petzsch, Klaus Pfeffer, Anne Tersteegen, Ursula R. Sorg, Julia Mock, Thomas Hehlgans, Karl Köhrer |
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| Rok vydání: | 2021 |
| Předmět: |
Lymphotoxin-beta
0301 basic medicine Clinical Biochemistry Population Biology Biochemistry Transcriptome 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Animals Hepatectomy education Molecular Biology education.field_of_study Liver cell Liver regeneration Liver Regeneration Cell biology 030104 developmental biology Lymphotoxin 030220 oncology & carcinogenesis Hepatocytes Tumor necrosis factor alpha Signal transduction Signal Transduction |
| Zdroj: | Biological Chemistry. 402:1147-1154 |
| ISSN: | 1437-4315 1431-6730 |
| Popis: | Lymphotoxin-β-receptor deficient (LTβR−/−) and Tumor Necrosis Factor Receptor p55 deficient (TNFRp55−/−) mice show defects in liver regeneration (LR) after partial hepatectomy (PHx) with significantly increased mortality. LTβR and TNFRp55 belong to the core members of the TNF/TNFR superfamily. Interestingly, combined failure of LTβR and TNFRp55 signaling after PHx leads to a complete defect in LR. Here, we first addressed the question which liver cell population crucially requires LTβR signaling for efficient LR. To this end, mice with a conditionally targeted LTβR allele (LTβRfl/fl) were crossed to AlbuminCre and LysozymeMCre mouse lines to unravel the function of the LTβR on hepatocytes and monocytes/macrophages/Kupffer cells, respectively. Analysis of these mouse lines clearly reveals that LTβR is required on hepatocytes for efficient LR while no deficit in LR was found in LTβRfl/fl × LysMCre mice. Second, the molecular basis for the cooperating role of LTβR and TNFRp55 signaling pathways in LR was investigated by transcriptome analysis of etanercept treated LTβR−/− (LTβR−/−/ET) mice. Bioinformatic analysis and subsequent verification by qRT-PCR identified novel target genes (Cyclin-L2, Fas-Binding factor 1, interferon-related developmental regulator 1, Leucyl-tRNA Synthetase 2, and galectin-4) that are upregulated by LTβR/TNFRp55 signaling after PHx and fail to be upregulated after PHx in LTβR−/−/ET mice. |
| Databáze: | OpenAIRE |
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