Liver Zonation Occurs Through a β-Catenin–Dependent, c-Myc–Independent Mechanism

Burke, Zoë D.; Reed, Karen Ruth; Phesse, Toby J.; Sansom, Owen J.; Clarke, Alan R.; Tosh, David

doi:10.1053/j.gastro.2009.02.063

Cited by 146 publications

(146 citation statements)

References 40 publications

Supporting

Mentioning

139

Contrasting

Order By: Relevance

“…However, using a human primary hepatocyte culture system that allows efficient infection with intact HCV virions [15] , and by blocking C/EBPβ Thr266 phosphorylation with a designed inhibitory dominant negative peptide [7] , we were able to demonstrate a causal effect of C/EBPβ Thr266 phosphorylation on hepatocyte proliferation and the zone-3 phenotype [14] . As previously reported [10][11][12] , we found that both β-Catenin and HIF-1α were expressed in a small acinar zone-3 in the liver from healthy controls (Figure 2A). We have determined that HCV infections expand the expression of β-Catenin and HIF-1α in non-cirrhotic livers and to a larger degree in cirrhotic livers (Figures 2A and 2B).…”

Section: Discussionsupporting

confidence: 87%

“…APC and β-Catenin modulate the liver acinar zonation and HIF-1α is induced by hypoxia [10][11][12] . Therefore, we analyzed whether HCV infection affects the expression of β-Catenin in zone-3 and whether the HCV infection affects the predictable expression of HIF-1α in the hypoxic acinar zone-3 [10][11][12] . We found that both β-Catenin and HIF-1α were expressed in a small acinar zone-3 in the liver from healthy controls (Figure 2A).…”

Section: Resultsmentioning

confidence: 99%

“…These values are reported as fold-increase from control samples. At least 100 cells were analyzed per experimental point [11,12] . These counts were performed with the tissue counting software from Keyence BZ-9000.…”

Section: Microscopy Analysismentioning

confidence: 99%

“…hepatocytes are characterized by the expression of Glutamine Synthetase (GS), β-Catenin and Hypoxia-Inducible Factor (HIF)-1 [9][10][11][12] . Expression of the GS gene in liver acinar zone-3 hepatocytes is stimulated by C/EBPβ [13] .…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Hepatitis C Virus Infection in Patients is Associated With C/ EBPβ-Thr266 Phosphorylation and Hepatocyte Proliferation

Traykova

Chojkier

Buck

2016

Journal of Gastroenterology and Hepatology Research

View full text Add to dashboard Cite

RESULTS:In patients with HCV infection, the HCV Core protein was preferentially co-localized with hepatocytes expressing Glutamine synthetase, phosphorylated C/EBPβ-Thr266, HIF-1α and β-Catenin. As expected, phosphorylated C/EBPβ-Thr266 was associated with hepatocyte proliferation in these patients. HCV infection markedly increased hepatocyte proliferation. CONCLUSION: This study demonstrates that HCV infection is preferentially localized to an expanded acinar zone expressing GS, where enhanced hepatocyte proliferation occurs in association with phosphorylated C/EBPβ-Thr266. A better understanding of the mechanisms of HCV infection may facilitate additional studies and potential therapeutic interventions. ABSTRACT AIM: Hepatitis C virus (HCV) infection in patients induces hepatocyte proliferation and also hepatocellular carcinoma. The mechanisms and the liver acinar distribution of the HCV infection remain unclear. The aim of this study was to determine the liver acinar localization of the infectious HCV and whether HCV infection is associated with the expression of proteins known to modulate hepatocyte proliferation. METHODS: We analyzed normal (n = 6), HCV genotype 1-infected non cirrhotic (n = 6) and HCV genotype 1-infected cirrhotic liver samples (n = 6). We performed immunofluorescent studies using antibodies against HCV Core, Glutamine synthetase (as a marker of hepatic acinar zone-3 in normal livers); phosphorylated C/EBPβ-Thr266 (since it is required for Transforming Growth Factorα-and Hepatic Growth Factor -induced hepatocyte proliferation) and ki-67 (as an indicator of hepatocyte proliferation). Also, we analyzed by QRT-PCR a proliferation microarray to compare the expression of genes associated with cell proliferation in HCV-infected patients.

show abstract

Section: Discussionsupporting

confidence: 87%

Section: Resultsmentioning

confidence: 99%

Section: Microscopy Analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Hepatitis C Virus Infection in Patients is Associated With C/ EBPβ-Thr266 Phosphorylation and Hepatocyte Proliferation

Traykova

Chojkier

Buck

2016

Journal of Gastroenterology and Hepatology Research

View full text Add to dashboard Cite

show abstract

“…In hepatoblastoma, however, previous studies have found no correlation between elevated Wnt activity and MYC expression in normal liver cells or hepatoblastoma cells, which implies that this gene is most likely not a Wnt target gene in this context (30,40,41). Furthermore, converging studies showed that Wnt target genes are cell-and context-specific (42).…”

Section: The Canonical Wnt Signaling Pathwaymentioning

confidence: 95%

Therapeutic Innovations for Targeting Hepatoblastoma

Garnier

Ilmer

Kappler

et al. 2016

View full text Add to dashboard Cite

Neutrophil and macrophage crosstalk might be a potential target for liver regeneration

Chen,

Yang,

et al. 2024

FEBS Open Bio

View full text Add to dashboard Cite

The regenerative capability of the liver is remarkable, but further research is required to understand the role that neutrophils play in this process. In the present study, we reanalyzed single‐cell RNA sequencing data from a mouse partial hepatectomy (PH) model to track the transcriptional changes in hepatocytes and non‐parenchymal cells. Notably, we unraveled the regenerative capacity of hepatocytes at diverse temporal points after PH, unveiling the contributions of three distinct zones in the liver regeneration process. In addition, we observed that the depletion of neutrophils reduced the survival and liver volume after PH, confirming the important role of neutrophils in liver regeneration. CellChat analysis revealed an intricate crosstalk between neutrophils and macrophages promoting liver regeneration and, using weighted gene correlation network analysis, we identified the most significant genetic module associated with liver regeneration. Our study found that hepatocytes in the periportal zone of the liver are more active than in other zones, suggesting that the crosstalk between neutrophils and macrophages might be a potential target for liver regeneration treatment.

show abstract

Liver Zonation Occurs Through a β-Catenin–Dependent, c-Myc–Independent Mechanism

Cited by 146 publications

References 40 publications

Hepatitis C Virus Infection in Patients is Associated With C/ EBPβ-Thr266 Phosphorylation and Hepatocyte Proliferation

Hepatitis C Virus Infection in Patients is Associated With C/ EBPβ-Thr266 Phosphorylation and Hepatocyte Proliferation

Therapeutic Innovations for Targeting Hepatoblastoma

Neutrophil and macrophage crosstalk might be a potential target for liver regeneration

Contact Info

Product

Resources

About