Epidermal Growth Factor: Its Biologic and Metabolic Effects With Emphasis on the Hepatocyte

Hilaire, R. James St.; Jones, Albert L.

doi:10.1002/hep.1840020515

Cited by 60 publications

(5 citation statements)

References 148 publications

(117 reference statements)

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“…For instance, consistent with earlier reports, our analysis predicted hepatocytes to receive prominent HGF/MET signaling from LSECs and stellate cells (Furge et al, 2000;LeCouter et al, 2003;Maher, 1993;Schirmacher et al, 1992). We did not capture an EGF-signaling network among different cell types, which is in agreement with low EGF expression in hepatic cells (Figure 5figure supplement 1C) and its predominantly exogenous origin (Olsen et al, 1985;St Hilaire and Jones, 1982;St Hilaire et al, 1983). However, we detected prominent heparin binding (HB)-EGF signaling from Kupffer cells and LSECs and other NPC populations (Kiso et al, 1995;.…”

Section: Rewiring Of Gene Regulatory Network Activates Cell State Transitions During Regenerationsupporting

confidence: 89%

Cellular plasticity balances the metabolic and proliferation dynamics of a regenerating liver

et al. 2021

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The adult liver has exceptional ability to regenerate, but how it sustains normal metabolic activities during regeneration remains unclear. Here, we use partial hepatectomy (PHx) in tandem with single-cell transcriptomics to track cellular transitions and heterogeneities of ~22,000 liver cells through the initiation, progression, and termination phases of mouse liver regeneration. Our results reveal that following PHx, a subset of hepatocytes transiently reactivates an early-postnatal-like gene expression program to proliferate, while a distinct population of metabolically hyperactive cells appears to compensate for any temporary deficits in liver function. Importantly, through combined analysis of gene regulatory networks and cellcell interaction maps, we find that regenerating hepatocytes redeploy key developmental gene regulons, which are guided by extensive ligand-receptor mediated signaling events between hepatocytes and non-parenchymal cells. Altogether, our study offers a detailed blueprint of the intercellular crosstalk and cellular reprogramming that balances the metabolic and proliferation requirements of a regenerating liver..

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Section: Rewiring Of Gene Regulatory Network Activates Cell State Transitions During Regenerationsupporting

confidence: 89%

Cellular plasticity balances the metabolic and proliferation dynamics of a regenerating liver

et al. 2021

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“…Although EGF is produced by multiple tissues, the two shown most relevant to liver regeneration include the Brunner’s glands in the duodenum and salivary glands. The Brunner’s glands provide a tonic supply of EGF via the portal circulation to the liver, where it is taken up and sequestered in the portal triad areas [76,77]. Increased circulating norephinephrine, as is seen after PHx, can augment Brunner’s glands secretion of EGF [78].…”

Section: Molecular Signals During Liver Regeneration After Phxmentioning

confidence: 99%

Signals and Cells Involved in Regulating Liver Regeneration

Kang

Mars

Michalopoulos

2012

Cells

124

105

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Liver regeneration is a complex phenomenon aimed at maintaining a constant liver mass in the event of injury resulting in loss of hepatic parenchyma. Partial hepatectomy is followed by a series of events involving multiple signaling pathways controlled by mitogenic growth factors (HGF, EGF) and their receptors (MET and EGFR). In addition multiple cytokines and other signaling molecules contribute to the orchestration of a signal which drives hepatocytes into DNA synthesis. The other cell types of the liver receive and transmit to hepatocytes complex signals so that, in the end of the regenerative process, complete hepatic tissue is assembled and regeneration is terminated at the proper time and at the right liver size. If hepatocytes fail to participate in this process, the biliary compartment is mobilized to generate populations of progenitor cells which transdifferentiate into hepatocytes and restore liver size.

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“…An increasing ER concentration was shown to be associated with tumor promotion, suggesting that the clonal expansion of preneoplastic liver cells requires ERs. Furthermore, EE 2 was shown to increase EGFR number and binding of EGF (known to be a potent mitogen for liver), which suggests that this is one of the mechanisms by which EE 2 may contribute to clonal expansion of initiated cells [59][60][61].…”

Section: Estrogens Ers and Hepatic Carcinogenesismentioning

confidence: 99%

Role of Estrogen in Liver Cancer

Villa

2008

Womens Health (Lond Engl)

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Liver cancer is the fifth most common cancer worldwide and despite increasing implementation of ultrasonographic surveillance strategies, its incidence is rising, especially in western countries. A universal characteristic of hepatocellular carcinoma is the striking male prevalence that is found, with few exceptions, both in animals and in humans. Many different hypotheses have been put forward in an attempt to explain this finding, which is not a simple epidemiological oddity but could also have pathogenetic implications. An obvious trail to follow, as gender susceptibility is implicated, is the role played by sex hormones, namely estrogens. Estrogens are not simply involved in reproductive mechanisms; instead, it is increasingly evident that they have a role in such an enormous variety of cellular processes that their implication in liver carcinogenesis may be manifold. The purpose of this review is to provide an overview of the available data, with a special focus on the hormonal mechanisms potentially implicated in the development of liver cancer.

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Epidermal Growth Factor: Its Biologic and Metabolic Effects With Emphasis on the Hepatocyte

Cited by 60 publications

References 148 publications

Cellular plasticity balances the metabolic and proliferation dynamics of a regenerating liver

Cellular plasticity balances the metabolic and proliferation dynamics of a regenerating liver

Signals and Cells Involved in Regulating Liver Regeneration

Role of Estrogen in Liver Cancer

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