Bile acid flux is necessary for normal liver regeneration
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE54673 | GEO | 2014/02/05
SECONDARY ACCESSION(S): PRJNA237324
REPOSITORIES: GEO
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Project description:Bile acid return from the intestine and attendant signaling is necessary for liver regeneration after partial hepatectomy or CCl4 injury Three groups of rat liver were examined at 4 time points (0, 4h, 12h, 24h) after partial hepatectomy; RNA from whole rat liver was isolated and deep sequencing was performed using the Illumina TruSeq platform
2014-02-05 | E-GEOD-54673 | biostudies-arrayexpress
Project description:Background & aimsMany signals governing liver regeneration (LR) following 2/3 partial hepatectomy (PH) are recognized, but the primary signal(s) remains unknown. The aim of the study was to confirm that the remnant liver after PH lacks capacity to secrete the BA pool returning via the enterohepatic ciruculation (EHC), which may in turn stimulate LR.MethodsAfter standard PH, BA flux was documented and BA signaling (Fgf15) and synthesis (Cyp7a) determined by qPCR. Rat biliary fistula (BF) and Asbt knockout mouse models interrupted the EHC prior to PH, and standard assays for LR employed along with complete RNA sequencing. CCl4 intoxication after BF tested the hypothesis in an alternate injury model.ResultsBA rise in systemic blood immediately following PH, confirming that the remnant liver cannot handle the BA returning via portal circulation. When the BA pool is drained prior to PH in the rat BF model, LR is markedly attenuated, a phenomenon reversed with duodenal BA replacement. Hepatocyte proliferation is similarly attenuated after PH in the Asbt knockout mouse as well as after CCl44 intoxication in rats with BF. Complete RNA sequencing in the rat PH model shows that early c-jun and AP-1 gene expression pathways are down regulated in the absence of BA, coincident with attenuated LR.ConclusionsAbsent BA return to the liver after PH or CCl4 injury markedly attenuates LR, though hepatocyte proliferation still occurs, inferring that BA flux and signaling are not the sole signals governing LR. Transcriptional networks involving c-jun and AP-1 are involved in the BA-specific effects on hepatocyte proliferation.
| S-EPMC4026228 | biostudies-literature
Project description:TGFβ/BMP family member Bone Morphogenetic Protein 8b (Bmp8b) is upregulated in NASH (Western Diet -WD- Model), acute liver damage (CCl4 model) and by Partial Hepatectomy (PH). Absence of Bmp8b reduces liver inflammation and fibrosis in the NASH model (WD). In the acute (3days) CCl4 model, absence of Bmp8b impacts acute inflammatory responses, hepatic stellate cells (HSC) activation, and compensatory hepatocyte proliferation; defective inflammatory pathways and hepatocytes proliferation is also observed in the Partial hepatectomy model. BMP8b is thus a pathophysiologically relevant target to modulate the responses to damage in acute and chronic liver disease.
2020-04-01 | GSE110404 | GEO
Project description:The scope of this project is to study, using state-of-the-art systems biology approaches integrating the changes in metabolomics, lipidomics and transcriptomics, changes in hepatocytes' metabolism occurring in liver regeneration. We focused on altered metabolic pathways including lipogenesis, fatty acid desaturation, and generation of phosphatidylcholine (PC) occurring in the liver following partial hepatectomy (PH) or carbon-tetrachloride (CCl4) injection.
2020-05-28 | GSE140461 | GEO
Project description:The study examined the role of TNF alpha in regulation of liver regeneration. For this purpose animals were divided in three groups of healthy controls, 2/3 partial hepatectomy alone, and animals pretreated with TNF alpha antagonist followed by 2/3 partial hepatectomy. Liver regeneration responses were then examined in conjunction with gene expression analysis at the peak of partial hepatectomy induced DNA synthesis. Substantive differences were identified in multiple gene ontology groups and cellular events and processes to indicate that TNF alpha was deleterious for partial hepatectomy induced liver regeneration.
2020-07-01 | GSE77888 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE20425: Hepatic gene expression during liver regeneration in response to partial hepatectomy: early time points (0.5h,1h,2h,4h) GSE20426: Hepatic gene expression during liver regeneration in response to partial hepatectomy: late time points (24h, 38h, 48h) Refer to individual Series
2011-02-16 | E-GEOD-20427 | biostudies-arrayexpress
Project description:Small noncoding (snc) RNAs represent a growing family of transcripts that regulate key cellular processes, including mRNA degradation, translational repression and transcriptional gene silencing. Among these, the PIWI-interacting RNAs (piRNAs), a major class of sncRNAs initially identified in the germline of a variety of species, are now being found to be functionally active also in somatic cells. However, whether the Piwi/piRNA pathway is associated with fundamental biological processes, such as cell cycle progression, remains elusive. Here we investigated the possibility that piRNAs are expressed in liver and modulated during regenerative proliferation of this organ. To this aim, smallRNA-Seq was applied to identify and quantitate expression of these RNAs in rat liver before, during and after the wave of cell proliferation that follows partial hepatectomy (PH). Q-PCR analysis revealed the presence in rat liver of two PIWI (PIWI-Like) subfamily members (PIWIL2/HILI and, to a much lower level, PIWIL4/HIWI2) and other components of the piRNA biogenesis pathways, suggesting that this is present and functional in hepatocytes. Indeed, ~1400 piRNAs originally identified in rat and other mammalian germline cells are expressed in adult rat liver, including 72 that show timed changes in expression during cell cycle progression. Most piRNAs are up-regulated 24-48h after hepatectomy, a timing that corresponds to cell transition through the S phase, and return to basal levels by 168 h, when organ regeneration is completed and hepatocytes reach quiescence. These results indicate that the piRNA pathway is active in somatic cells and, more important, that it is subject to regulation during physiological processes, such as cell proliferation, when piRNAs may exert their regulatory functions on the cell genome and transcriptome. smallRNA-Seq was applied to identify and quantitate expression of RNAs in rat liver before and after partial hepatectomy (PH).
2014-06-17 | E-GEOD-55783 | biostudies-arrayexpress
Project description:Background and aims: The Hippo pathway and its downstream effectors YAP and TAZ (YAP/TAZ) are heralded as important regulators of organ growth and regeneration. However, different studies provided contradictory conclusions about their role during regeneration of different organs ranging from promoting proliferation to inhibiting it. Here, we resolve the function of YAP/TAZ during regeneration of the liver, where Hippo’s role in growth control has been studied most intensely. Methods: We evaluated liver regeneration after CCl4 toxic liver injury in mice with conditional deletion of Yap/Taz in hepatocytes and/or biliary epithelial cells and measured the behavior of different cell types during regeneration by histology, RNA-sequencing and flow cytometry. Results: We found that YAP/TAZ were activated in hepatocytes in response to CCl4 toxic injury. However, their targeted deletion in adult hepatocytes did not noticeably impair liver regeneration. In contrast, Yap/Taz deletion in adult bile ducts caused severe defects and delay in liver regeneration. Mechanistically, we show that Yap/Taz mutant bile ducts degenerated, causing cholestasis which stalled the recruitment of phagocytic macrophages and the removal of cellular corpses from injury sites. Elevated bile acids activated PXR, which was sufficient to recapitulate the phenotype observed in mutant mice. Conclusions: Our data show that YAP/TAZ are practically dispensable in hepatocytes for liver development and regeneration. Rather, YAP/TAZ play an indirect role in liver regeneration by preserving bile duct integrity and securing immune cell recruitment and function.
2020-11-02 | GSE157088 | GEO
Project description:In this study, we compared different liver cell populations in normal and partial hepatectomy mouse model.
2024-02-23 | GSE226004 | GEO
Project description:The recovery of liver mass is mainly mediated by proliferation and enlargement of hepatocytes after partial hepatectomy. Studying the gene expression profiles of hepatocytes after partial hepatectomy will be helpful in exploring the mechanism of liver regeneration. We used microarrays to further highlight the regulatory role of hepatocyte in liver regeneration at gene transcription level.
2014-02-28 | GSE55434 | GEO