Speeding up hepatocyte proliferation: How triiodothyronine and β-catenin join forces

Gebhardt, Rolf

doi:10.1002/hep.26984

Cited by 8 publications

(4 citation statements)

References 20 publications

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“…It is important to identify factors that regulate β -catenin activity. We have shown that triiodothyronine can activate β -catenin in cells 40,145 and studies in animals are planned.…”

Section: Future Directionsmentioning

confidence: 99%

β-Catenin Signaling and Roles in Liver Homeostasis, Injury, and Tumorigenesis

2015

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β -catenin (encoded by CTNNB1) is a subunit of the cell surface cadherin protein complex that acts as an intracellular signal transducer in the WNT signaling pathway; alterations in its activity have been associated with the development of hepatocellular carcinoma and other liver diseases. Other than WNT, additional signaling pathways also can converge at β-catenin. β-catenin also interacts with transcription factors such as T-cell factor, forkhead box protein O, and hypoxia inducible factor 1α to regulate the expression of target genes. We discuss the role of β-catenin in metabolic zonation of the adult liver. β-catenin also regulates the expression of genes that control metabolism of glucose, nutrients, and xenobiotics; alterations in its activity may contribute to the pathogenesis of nonalcoholic steatohepatitis. Alterations in β-catenin signaling may lead to activation of hepatic stellate cells, which is required for fibrosis. Many hepatic tumors such as hepatocellular adenomas, hepatocellular cancers, and hepatoblastomas have mutations in CTNNB1 that result in constitutive activation of β-catenin, so this molecule could be a therapeutic target. We discuss how alterations in β-catenin activity contribute to liver disease and how these might be used in diagnosis and prognosis, as well as in the development of therapeutics.

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“…It is important to identify factors that regulate β -catenin activity. We have shown that triiodothyronine can activate β -catenin in cells 40,145 and studies in animals are planned.…”

Section: Future Directionsmentioning

confidence: 99%

β-Catenin Signaling and Roles in Liver Homeostasis, Injury, and Tumorigenesis

2015

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“…Indeed, agents such as triiodothyronine or thyroid receptor-β agonists like GC-1 may have clinical applications in settings of hepatic insufficiency. 84–86 …”

Section: Discussionmentioning

confidence: 99%

Update on the Mechanisms of Liver Regeneration

Preziosi

Monga

2017

Semin Liver Dis

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Liver possesses many critical functions such as synthesis, detoxification, and metabolism. It continually receives nutrient-rich blood from gut, which incidentally is also toxin-rich. That may be why liver is uniquely bestowed with a capacity to regenerate. A commonly studied procedure to understand the cellular and molecular basis of liver regeneration is that of surgical resection. Removal of two-thirds of the liver in rodents or patients instigates alterations in hepatic homeostasis, which are sensed by the deficient organ to drive the restoration process. Although the exact mechanisms that initiate regeneration are unknown, alterations in hemodynamics and metabolism have been suspected as important effectors. Key signaling pathways are activated that drive cell proliferation in various hepatic cell types through autocrine and paracrine mechanisms. Once the prehepatectomy mass is regained, the process of regeneration is adequately terminated. This review highlights recent discoveries in the cellular and molecular basis of liver regeneration.

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“…The Hedgehog cascade may be triggered by HIF-1α through hypoxia consequent to hepatic resection (Bijlsma et al 2008). It is also worth to note that Hedgehog is a target of Wnt/βcatenin in the liver, suggesting a redox-dependent crosstalk between these pathways in regeneration following hepatic resection (Gebhardt 2014). The Hippo-YAP pathway is variably modulated by redox homeostasis, producing different functional outcomes.…”

Section: Redox Modulation Of Proliferation Pathwaysmentioning

confidence: 99%

Redox experimental medicine and liver regeneration

Bellanti

Vendemiale

Serviddio

2022

Redox Experimental Medicine

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The liver is characterized by unique regenerative properties to restore its mass and function after a partial loss. Hepatic regeneration arises after resection or following acute and chronic injuries. Resection and acute liver damage normally induce a regenerative process characterized by phenotypic fidelity, in which each cell type promotes its own replication and replacement. This process fails in chronic liver damage, where trans-differentiation of parenchymal cells or activation of facultative progenitors occurs. Both liver resection and acute/chronic damages alter redox homeostasis, as a consequence of blood flow changes, hypoxia, metabolism modification, and activation of inflammatory response. Even though formerly described as ‘oxidative stress’, altered redox homeostasis leads to the fine regulation of several pathways involved in liver regeneration, including the proliferation of parenchymal cells, trans-differentiation, and activation of facultative progenitors. Several redox-dependent transcription factors and pathways implicated in the regenerative process of the liver were described, but pre-clinical experiments using different antioxidants were not fully conclusive. Even though accurate study designs to define appropriate dosages, treatment duration, and routes of administration are required, modulation of redox-dependent molecular pathways to enhance liver regeneration is even more intriguing. Preliminary studies focused on the identification of these targets will pave the way for viable therapies to be tested in clinical trials.

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Speeding up hepatocyte proliferation: How triiodothyronine and β-catenin join forces

Cited by 8 publications

References 20 publications

β-Catenin Signaling and Roles in Liver Homeostasis, Injury, and Tumorigenesis

β-Catenin Signaling and Roles in Liver Homeostasis, Injury, and Tumorigenesis

Update on the Mechanisms of Liver Regeneration

Redox experimental medicine and liver regeneration

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