Sorg, Ursula R. and Kuepper, Nicole and Mock, Julia and Tersteegen, Anne and Petzsch, Patrick and Koehrer, Karl and Hehlgans, Thomas and Pfeffer, Klaus (2021) Lymphotoxin-beta-receptor (LT beta R) signaling on hepatocytes is required for liver regeneration after partial hepatectomy. BIOLOGICAL CHEMISTRY, 402 (9). pp. 1147-1154. ISSN 1431-6730, 1437-4315
Full text not available from this repository. (Request a copy)Abstract
Lymphotoxin-p-receptor deficient (LT beta R-/-) and Tumor Necrosis Factor Receptor p55 deficient (TNFRp55(-/-)) mice show defects in liver regeneration (LR) after partial hepatectomy (PHx) with significantly increased mortality. LT beta R and TNFRp55 belong to the core members of the TNF/TNFR superfamily. Interestingly, combined failure of LT beta R and TNFRp55 signaling after PHx leads to a complete defect in LR. Here, we first addressed the question which liver cell population crucially requires LT beta R signaling for efficient LR. To this end, mice with a conditionally targeted LT beta R allele (LT beta R-fl/fl) were crossed to AlbuminCre and Lysozy-meMCre mouse lines to unravel the function of the LT beta R on hepatocytes and monocytes/macrophages/Kupffer cells, respectively. Analysis of these mouse lines clearly reveals that LT beta R is required on hepatocytes for efficient LR while no deficit in LR was found in LT beta R-fl/fl x LysMCre mice. Second, the molecular basis for the cooperating role of LT beta R and TNFRp55 signaling pathways in LR was investigated by transcriptome analysis of etanercept treated LT beta R-/- (LT beta R-/-/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 LT beta R/TNFRp55 signaling after PHx and fail to be upregulated after PHx in LT beta R-/-/ET mice.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | NECROSIS-FACTOR-RECEPTOR; GENE-EXPRESSION; MICE LACKING; CYCLIN L2; MACROPHAGES; ACTIVATION; DEFICIENT; IDENTIFICATION; ORGANOGENESIS; SUPERFAMILY; AlbuminCre line; etanercept; LT beta R; partial hepatectomy; TNFRp55; transcriptome analysis |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Zentren des Universitätsklinikums Regensburg > Regensburger Centrum für Interventionelle Immunologie (RCI) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 13 Sep 2022 15:07 |
| Last Modified: | 13 Sep 2022 15:07 |
| URI: | https://pred.uni-regensburg.de/id/eprint/47375 |
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