Mitogenesis by ligands of nuclear receptors: an attractive model for the study of the molecular mechanisms implicated in liver growth

Columbano, Amedeo; Ledda-Columbano, Giovanna M.

doi:10.1038/sj.cdd.4401113

Cited by 50 publications

(54 citation statements)

References 16 publications

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“…1A). The hepatomegalic effect of 3-day treatment with PB is less pronounced than that exerted by the potent mitogen TCPOBOP in PBP ϩ/ϩ livers (20,21,26). DNA synthesis in liver is markedly increased in wild-type mice after TCPOBOP treatment ( Fig.…”

Section: Resultsmentioning

confidence: 92%

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Transcription coactivator peroxisome proliferator-activated receptor-binding protein/mediator 1 deficiency abrogates acetaminophen hepatotoxicity

Jia

Guo

Surapureddi

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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constitutive androstane receptor N uclear receptors constitute a large superfamily of transcription factors that regulate a diverse array of biological process, including development, differentiation, and neoplasia as well as energy and xenobiotic metabolism (1-3). The binding of specific ligands to nuclear receptors influences the recruitment of initial complex of coactivator proteins with histone acetyltransferase activity necessary for remodeling chromatin (1-3). Docking of several other cofactors results in the formation of a multiprotein coactivator complex, variously called thyroid hormone receptor-associated protein (TRAP)͞vitamin D receptorinteracting protein͞activator-recruited cofactor͞mediator complex, that facilitates interaction with RNA polymerase II and the general basal transcription machinery

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Section: Resultsmentioning

confidence: 92%

“…CAR mediates the response evoked by a class of xenobiotics referred to as the ''PB-like inducers'' (16,26). Short-term treatment with either PB or TCPOBOP increased liver mass in wild-type PBP ϩ/ϩ mice but not in PBP LivϪ/Ϫ mice (Fig.…”

Section: Resultsmentioning

confidence: 99%

Transcription coactivator peroxisome proliferator-activated receptor-binding protein/mediator 1 deficiency abrogates acetaminophen hepatotoxicity

Jia

Guo

Surapureddi

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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“…Nutrition and NEB effects on liver molecular adaptations In non-ruminants, the differentiation of hepatocytes and the function of the adult liver are controlled through the coordinated expression of a large number of genes (Columbano and Ledda-Columbano, 2003). Therefore, transcriptomics analyzed through bioinformatics tools are ideal to help identify regulatory mechanisms in the bovine liver that are sensitive to nutrient balance during the transition from pregnancy to lactation.…”

Section: Linking Cattle Genome To Ruminant Metabolismmentioning

confidence: 99%

Cattle genomics and its implications for future nutritional strategies for dairy cattle

Seo

Larkin

Loor

2013

Animal

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The recently sequenced cattle (Bos taurus) genome unraveled the unique genomic features of the species and provided the molecular basis for applying a systemic approach to systematically link genomic information to metabolic traits. Comparative analysis has identified a variety of evolutionary adaptive features in the cattle genome, such as an expansion of the gene families related to the rumen function, large number of chromosomal rearrangements affecting regulation of genes for lactation, and chromosomal rearrangements that are associated with segmental duplications and copy number variations. Metabolic reconstruction of the cattle genome has revealed that core metabolic pathways are highly conserved among mammals although five metabolic genes are deleted or highly diverged and seven metabolic genes are present in duplicate in the cattle genome compared to their human counter parts. The evolutionary loss and gain of metabolic genes in the cattle genome may reflect metabolic adaptations of cattle. Metabolic reconstruction also provides a platform for better understanding of metabolic regulation in cattle and ruminants. A substantial body of transcriptomics data from dairy and beef cattle under different nutritional management and across different stages of growth and lactation are already available and will aid in linking the genome with metabolism and nutritional physiology of cattle. Application of cattle genomics has great potential for future development of nutritional strategies to improve efficiency and sustainability of beef and milk production. One of the biggest challenges is to integrate genomic and phenotypic data and interpret them in a biological and practical platform. Systems biology, a holistic and systemic approach, will be very useful in overcoming this challenge.

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“…As the signal transduction pathways responsible for the transition from G0 to G1 phase of the hepatocytes in mitogen-induced direct hyperplasia are different from those classically associated to liver regeneration, 13 the results stemming from the above studies could have significant clinical relevance, as they suggest a potential therapeutic approach to relieve the proliferative block after liver injury that is observed in the elderly. Treatment with mitogens could also have applications in liver transplantation, gene therapy and hepatic failure.…”

Section: Xenobiotic Mitogens and Liver Regeneration A Columbano Et Almentioning

confidence: 99%

“…11 Activated nuclear receptors not only regulate genes involved in lipid metabolism, adipogenesis, xenobiotic detoxification and differentiation 12 but also stimulate hepatocyte proliferation. 13 Interestingly, early changes considered to be essential for liver regeneration after PH: [14][15][16] activation of the transcription factors activating protein-1 (AP-1), nuclear factor-kB, signal transducer activator of transcription 3 and C/enhancer-binding protein; increased expression of immediate early genes such as c-fos, c-jun, c-myc, liver regenerating factor-1, and early growth response-1 and release of the cytokines tumor-necrosis factor-a and interleukin-6 are not observed in nuclear receptor-mediated hepatocyte proliferation. 17,18 The early signal transduction pathways involved in nuclear receptor-mediated hepatocyte proliferation are, therefore, different from those involved in liver regeneration.…”

mentioning

confidence: 99%

Potential utility of xenobiotic mitogens in the context of liver regeneration in the elderly and living-related transplantation

Columbano¹,

Simbula²,

Pibiri³

et al. 2008

Laboratory Investigation

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Although liver regeneration occurring after partial hepatectomy (PH) is greatly reduced in aged mice, liver hyperplasia induced by xenobiotic mitogens was found to be age independent. Here, we investigated the potential utility of mitogens in stimulating liver regeneration in old mice subjected to two-third PH. Although virtually no hepatocytes entered S phase 48 h after PH, pretreatment (2 h prior to surgery) with 1,4-bis(2-(3,5-dichloropyridyloxy)benzene (TCPOBOP), a ligand of constitutive androstane receptor, induced an increase of bromodeoxyuridine incorporation and enhanced the expression of cyclin D1, cyclin A and proliferating cell nuclear antigen . Next, we investigated the potential utility of mitogens in the context of donor conditioning prior to living-related transplantation. Three days after TCPOBOP administration to intact young mice, an almost doubling of the liver mass and DNA content occurred; the regenerative response to two-third resection of the TCPOBOP-induced hyperplastic liver was similar to that of mice subjected to PH alone, suggesting that an increased liver mass at the time of surgery does not inhibit the regenerative capacity. The present results suggest that mitogen-induced hyperplasia is a promising tool in conditions characterized by reduced regenerative capacity, such as in the elderly, or when a rapid increase of liver mass is required, such as in living-related transplantation.

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Mitogenesis by ligands of nuclear receptors: an attractive model for the study of the molecular mechanisms implicated in liver growth

Cited by 50 publications

References 16 publications

Transcription coactivator peroxisome proliferator-activated receptor-binding protein/mediator 1 deficiency abrogates acetaminophen hepatotoxicity

Transcription coactivator peroxisome proliferator-activated receptor-binding protein/mediator 1 deficiency abrogates acetaminophen hepatotoxicity

Cattle genomics and its implications for future nutritional strategies for dairy cattle

Potential utility of xenobiotic mitogens in the context of liver regeneration in the elderly and living-related transplantation

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