Human hepatic progenitor cells express vasoactive intestinal peptide receptor type 2 and receive nerve endings

Cassiman, David; Sinelli, Nicoletta; Bockx, Ilse; Borght, Sara Vander; Petersen, Bryon E.; Vos, Rita De; Pelt, Jos van; Nevens, Frederik; Libbrecht, Louis; Roskams, Tania

doi:10.1111/j.1478-3231.2006.01427.x

Cited by 19 publications

(18 citation statements)

References 16 publications

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“…[11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27] These findings strongly suggest the close association between the present tumor and neural stem cells. [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27] It can be plausible that the present tumor arose from neural stem cells. That is, there is a possibility that the present tumor is a kind of stem cell tumor.…”

Section: Discussionsupporting

confidence: 52%

“…These findings suggest that stem cell factor/KIT, platelet-derived growth factor-alpha/PDGFRA, hepatocyte growth factor/MET, and epidermal growth factor/ErbB2 signaling pathways play an important role in the tumorigenesis and tumor growth in the present perineuroma. [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27] In the present case, CK14 (a stem cell antigen) was negative, suggesting that all stem cell markers are not expressed in the present possible stem cell tumors. The present tumor showed negative expression of CK AE1/3, CK CAM5.2 and EMA, indicating that the present tumor is not an epithelial tumor.…”

Section: Discussionmentioning

confidence: 73%

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Perineuroma of the skin negative for S100 protein but positive for stem cell antigens: A possible stem cell tumor

Terada

2016

CRCP

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Perineuroma is a rare tumor originating from perineurium of the peripheral nerve. In contrast to neurofibroma and schwannoma, both of which arise from endoneurium and are immunohistochemically positive for S100 protein, perineuroma is negative for S100 protein; the fact makes the pathologic diagnosis difficult. As is well known, stem cells are highly associated with neuronal and organ developments in human embryos, and some neuronal cells are suspected to be derived from neuronal stem cells. Herein reported a very rare case of subcutaneous perineuroma negative for S100 protein but positive for a number of stem cell antigens; the case suggested that some perineuromas could arise from neuronal stem cells. A 68-year-old woman presented with a skin tumor of 10 mm in diameter in the foot. Physical examination revealed a small movable subcutaneous tumor, and resection was performed. Histologically, the tumor was a well-defined round tumor measuring 0.9 cm × 0.9 cm × 0.9 cm located in the subcutaneous tissue. No capsule was seen. The tumor was composed of hypocellular myxoid, neuroid tissues containing small areas of high cellularity where tumor cells resembled neuronal stem cells. Immunohistochemically, the tumor was negative for S100 protein, HMB-45, various cytokeratin (CK), EMA, α-SMA, desmin, p53, and many other antigens. The neuronal stem cell-like cells were positive for various stem cell antigens including NSE, KIT, bcl-2, chromogranin, synaptophysin, PDGFRA, MET, ErbB2, and CD34, as well as for vimentin and Ki-67 antigen (labeling index = 1.5%). Because the tumor was negative for S100 protein but positive for neuroendocrine molecules and neuronal stem cell antigens, the author diagnosed the tumor as perineuroma with stem cell features. Such a perineuroma has not been reported to date. The outcome of the patient was excellent.

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Section: Discussionsupporting

confidence: 52%

Section: Discussionmentioning

confidence: 73%

Perineuroma of the skin negative for S100 protein but positive for stem cell antigens: A possible stem cell tumor

Terada

2016

CRCP

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“…on May 12, 2018 by guest http://jvi.asm.org/ and hematopoietic cells also express functional VIP receptors (6,7,35,82). While there are no published reports linking VIP to HCMV reactivation in vivo, this association is plausible based on the following considerations.…”

Section: Discussionmentioning

confidence: 99%

“…(4,16,32) in which HCMV also reactivates with greater frequency (26,33,40,43,51,80). VIP receptors are expressed on progenitors of neuronal, hepatic, retinal pigment epithelial, and hematopoietic cells (6,7,35,82). On the basis of this information, VIP was further studied in the HCMV reactivation model.…”

Section: Cells and Virusesmentioning

confidence: 99%

Breaking Human Cytomegalovirus Major Immediate-Early Gene Silence by Vasoactive Intestinal Peptide Stimulation of the Protein Kinase A-CREB-TORC2 Signaling Cascade in Human Pluripotent Embryonal NTera2 Cells

Yuan

Liu

et al. 2009

J Virol

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. We speculate that neurohormonal stimulation via this signaling cascade is a possible means for reversing HCMV silence in vivo.Persons with impaired cellular immunity risk tissue-invasive disease from reactivation of latent human cytomegalovirus (HCMV). HCMV reactivation in tissues or blood of immunocompetent patients suffering illness from another cause also occurs but usually goes unnoticed and is self-limiting. For instance, nearly one-third of patients who are critically ill or in septic shock have detectable findings of HCMV reactivation in their bloodstream (12,26,43,45,80). HCMV reactivation infection in intestinal tissues with preexisting inflammatory disease (e.g., inflammatory bowel disease) is also well described for immunocompetent patients (28,39,40,51). The precise triggering mechanisms that underlie HCMV reactivation are unknown.So far, only cells of myeloid lineage have been determined to fulfill criteria for cellular sites of HCMV latency in vivo. In healthy HCMV-seropositive persons, precursors of macrophages and dendritic cells, including CD34ϩ hematopoietic progenitor cells, carry latent HCMV genomes at a low frequency (75). The terminal differentiation of these cells into a macrophage-or dendritic cell-like phenotype is a prerequisite for HCMV reactivation ex vivo (67, 76). However, this reactivation appears to be a rare event, suggesting that other, as yet unidentified factors may promote HCMV reactivation. Stimulation with tumor necrosis factor alpha (TNF-␣) or gamma interferon may promote HCMV reactivation from differentiated counterparts of monocytic-dendritic cell precursors that had been infected latently in vitro or in vivo (25,66,67,76).For both HCMV and murine CMV, viral major immediateearly (MIE) gene expression is greatly restricted or shut off during viral latency, and the productive viral life cycle cannot advance without this expression (57,74,75,78). The MIE enhancer/promoter controlling expression is regulated by the coordinated actions of multiple types of cis-acting elements (57). These elements are bound by cellular transcription factors whose functions are modulated by input supplied by the cell, the virus, and the external surrounding (57). Higher-order chromatin structure contributes to this regulation. Heterochromatin components amass on the inactive MIE enhancer/promoter in viral latency, whereas the chromatin signatures of transcriptional activity predominate at the active MIE enhancer/ promoter in acute and reactivation infections (47,67). MIE enhancer/promoter silencing is also favored by innate antiviral mechanisms that partly involve the repressive actions of nuclear ND10 domain components (e.g., hDAXX, PML, ATRX, and histone deacetylase [HDAC]) (52) but does not involve CpG methylation of the MIE enhancer/promoter (29).Quiescent HCMV infection of human NTera2/D1 cells (NT2 cells) is a tractable model system for studying the regulation of HCMV MIE enhancer/promoter reactivation (37, 54). NT2 cells share many phenotypic features with pluripotent

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“…Specifically, sympathetic neural input inhibition reduces hepatocyte injury and promotes oval cell proliferation (Oben and Diehl, 2004). Finally, oval cells were shown to express vasoactive intestinal peptide (VIP) receptors and receive input from VIP-containing neurons (Miyazawa et al, 1988;Akiyoshi et al, 1998;Cassiman et al, 2007). Hence, in addition to acetylcholine, the vagus nerve stores and releases other neurotransmitters, including VIP that may modulate liver injury responses.…”

Section: Discussionmentioning

confidence: 99%

Scopolamine Treatment and Muscarinic Receptor Subtype-3 Gene Ablation Augment Azoxymethane-Induced Murine Liver Injury

Khurana

Shah

Cheng

et al. 2010

J Pharmacol Exp Ther

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Previous work suggests that vagus nerve disruption reduces hepatocyte and oval cell expansion after liver injury. The role of postneuronal receptor activation in response to liver injury has not been ascertained. We investigated the actions of scopolamine, a nonselective muscarinic receptor antagonist, and specific genetic ablation of a key cholinergic receptor, muscarinic subtype-3 (Chrm3), on azoxymethane (AOM)-induced liver injury in mice. Animal weights and survival were measured as was liver injury using both gross and microscopic examination. To assess hepatocyte proliferation and apoptosis, ductular hyperplasia, and oval cell expansion, we used morphometric analysis of 5-bromo-2Ј-deoxyuridine-, activated caspase-3-, hematoxylin and eosin-, cytokeratin-19-, and epithelial cell adhesion molecule-stained liver sections. Sirius red staining was used as a measure of collagen deposition and its association with oval cell reaction. In AOM-treated mice, both muscarinic receptor blockade with scopolamine and Chrm3 ablation attenuated hepatocyte proliferation and augmented gross liver nodularity, apoptosis, and fibrosis. Compared with control, scopolamine-treated and Chrm3(Ϫ/Ϫ) AOM-treated mice had augmented oval cell reaction with increased ductular hyperplasia and oval cell expansion. Oval cell reaction correlated robustly with liver fibrosis. No liver injury was observed in scopolamine-treated and Chrm3(Ϫ/Ϫ) mice that were not treated with AOM. Only AOMtreated Chrm3(Ϫ/Ϫ) mice developed ascites and had reduced survival compared with AOM-treated wild-type controls. In AOMinduced liver injury, inhibiting postneuronal cholinergic muscarinic receptor activation with either scopolamine treatment or Chrm3 gene ablation results in prominent oval cell reaction. We conclude that Chrm3 plays a critical role in the liver injury response by modulating hepatocyte proliferation and apoptosis.Acetylcholine activates two classes of cholinergic receptors: nicotinic, which function as cation channels, and muscarinic (CHRM), which mediate G protein-coupled signaling. Five mammalian CHRM subtypes (CHRM1-5) are described; oddnumbered CHRM (CHRM1, 3, and 5) preferentially activate G q/11 proteins, whereas even-numbered CHRM (CHRM2 and 4) activate G i/o proteins. Cell type-specific expression of CHRM subtypes mediates diverse signaling events. In the nervous system, muscarinic receptors play a major role in synaptic transmission and regulate sensory, motor, and autonomic functions. In non-neuronal tissue, muscarinic receptor activation regulates cell function (Shah et al., 2009). For example, muscarinic receptors mediate proliferation of lung and colon cancer cells (Raufman et al., 2008;Shah et al., 2009).In the liver, stimulation of the vagus nerve induces proliferation of oval cells (designated intermediate hepatobiliary Article, publication date, and citation information can be found at

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Human hepatic progenitor cells express vasoactive intestinal peptide receptor type 2 and receive nerve endings

Abstract: We show here for the first time that HPC express VIPR2 and receive nerve endings. These features, and the fact that HPC numbers are influenced by the presence or absence of the autonomic innervation of the liver, suggest a direct interaction.

Cited by 19 publications

References 16 publications

Perineuroma of the skin negative for S100 protein but positive for stem cell antigens: A possible stem cell tumor

Perineuroma of the skin negative for S100 protein but positive for stem cell antigens: A possible stem cell tumor

Breaking Human Cytomegalovirus Major Immediate-Early Gene Silence by Vasoactive Intestinal Peptide Stimulation of the Protein Kinase A-CREB-TORC2 Signaling Cascade in Human Pluripotent Embryonal NTera2 Cells

Scopolamine Treatment and Muscarinic Receptor Subtype-3 Gene Ablation Augment Azoxymethane-Induced Murine Liver Injury

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