Glial Fibrillary Acidic Protein (GFAP)-like Immunoreactivity in Rat Endocrine Pancreas

Regoli, Marì; Orazioli, Daniela; Gerli, R; Bertelli, Eugenio

doi:10.1177/002215540004800211

Cited by 17 publications

(16 citation statements)

References 47 publications

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“…It has been reported that α-cells of the Langerhans islets express GFAP [21,22]. As these α-cells are the main source of glucagon and tumor-bearing LSL-MYCN;hGFAP-Cre mice displayed with elevated blood glucagon levels as well as Glucagon-positive tumors, these findings are in line with the diagnosis of a glucagon-producing PanNET.…”

Section: Discussionsupporting

confidence: 61%

Characterization of pancreatic glucagon-producing tumors and pituitary gland tumors in transgenic mice overexpressingMYCNinhGFAP-positive cells

et al. 2016

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Amplification or overexpression of MYCN is involved in development and maintenance of multiple malignancies. A subset of these tumors originates from neural precursors, including the most aggressive forms of the childhood tumors, neuroblastoma and medulloblastoma. In order to model the spectrum of MYCN-driven neoplasms in mice, we transgenically overexpressed MYCN under the control of the human GFAP-promoter that, among other targets, drives expression in neural progenitor cells. However, LSL-MYCN;hGFAP-Cre double transgenic mice did neither develop neural crest tumors nor tumors of the central nervous system, but presented with neuroendocrine tumors of the pancreas and, less frequently, the pituitary gland. Pituitary tumors expressed chromogranin A and closely resembled human pituitary adenomas. Pancreatic tumors strongly produced and secreted glucagon, suggesting that they derived from glucagon- and GFAP-positive islet cells. Interestingly, 3 out of 9 human pancreatic neuroendocrine tumors expressed MYCN, supporting the similarity of the mouse tumors to the human system. Serial transplantations of mouse tumor cells into immunocompromised mice confirmed their fully transformed phenotype. MYCN-directed treatment by AuroraA- or Brd4-inhibitors resulted in significantly decreased cell proliferation in vitro and reduced tumor growth in vivo. In summary, we provide a novel mouse model for neuroendocrine tumors of the pancreas and pituitary gland that is dependent on MYCN expression and that may help to evaluate MYCN-directed therapies.

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Section: Discussionsupporting

confidence: 61%

Characterization of pancreatic glucagon-producing tumors and pituitary gland tumors in transgenic mice overexpressingMYCNinhGFAP-positive cells

et al. 2016

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“…Islet cells likely evolved from an ancestral neuronal precursor and have inherited a diverse set of proteins that, in the central nervous system, provide the machinery for cell-to-cell signaling across synapses (Donev 1984, Regoli et al 2000, Rulifson et al 2002. These proteins include GAD65, GAD67, GABA receptors, glutamate and glycine receptors and vesicular glutamate and GABA transporters (Satin & Kinard 1998, Chessler et al 2002, Hayashi et al 2003b, Gammelsaeter et al 2004.…”

Section: Discussionmentioning

confidence: 99%

Identification and characterization of a novel isoform of the vesicular γ-aminobutyric acid transporter with glucose-regulated expression in rat islets

Suckow

Sweet

Yserloo

et al. 2006

Journal of Molecular Endocrinology

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Pancreatic islets are unique outside the nervous system in that they contain high levels of the inhibitory neurotransmitter -aminobutyric acid (GABA), synthesized by the enzyme glutamic acid decarboxylase (GAD). Since the role that GABA plays in the islet and the mechanisms whereby the two major GAD isoforms (GAD65 and GAD67) function as diabetes-associated autoantigens are unknown, continued characterization of the islet GAD-GABA system is important. We previously demonstrated that the GABA and glycine transporter vesicular inhibitory amino acid transporter (VIAAT also known as VGAT) is present in rat islets. Here we identify a novel 52 kDa variant of VIAAT in rat islets: VIAAT-52 (V52). V52 is an amino-terminally truncated form of VIAAT (V57) that likely results from utilization of a downstream start site of translation. V57 and V52 display different patterns of post-translational modification and cellular expression. Our results have indicated that islet content of V52, but not V57, is responsive to changes in glucose concentration and other extracellular conditions. VIAAT is expressed in the islet cells, but there have been conflicting findings regarding the presence of VIAAT in the cells. Here we have also provided additional evidence for the presence of VIAAT in islet cells and show that the cell line INS-1 expresses V57. V52 may be better adapted than V57 to the unique rat cell GAD-GABA system, which lacks GAD65 and in which VIAAT traffics to secretory granules rather than just to synaptic microvesicles.

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“…Again available evidence argues against this notion. Numerous cells outside the nervous system express GFAP, including hepatic stellate cells, mesangial cells in kidney, and specialized cells in lung, pancreas, bone marrow, and other tissues (Viale et al, 1988;Neubauer et al, 1996;Buniatian et al, 1998;Bush et al, 1998;Regoli et al, 2000). Within the nervous system, GFAP is expressed by numerous developing and mature cells that are not considered astrocytes, including Schwann cells, satellite cells, enteric glia, ependymal cells, radial glia, tanycytes, M€ uller cells, and others (Levitt and Rakic, 1980;Jessen et al, 1990;Bush et al, 1998).…”

Section: Heterogeneity Of Gfap-expressing Cells Inmentioning

confidence: 99%

Phenotypic and functional heterogeneity of GFAP‐expressing cells in vitro: Differential expression of LeX/CD15 by GFAP‐expressing multipotent neural stem cells and non‐neurogenic astrocytes

Imura

Nakano

Kornblum

et al. 2005

Glia

107

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Recent findings show that the predominant multipotent neural stem cells (NSCs) isolated from postnatal and adult mouse brain express glial fibrillary acid protein (GFAP), a protein commonly associated with astrocytes, and that primary astrocyte cultures can contain GFAP-expressing cells that act as multipotent NSCs when transferred to neurogenic conditions. The relationship of GFAP-expressing NSCs to GFAP-expressing astrocytes is unclear, but has important implications. We compared the phenotype and neurogenic potential of GFAP-expressing cells derived from different CNS regions and maintained in vitro under different conditions. Multiple labeling immunohistochemistry revealed that both primary astrocyte cultures and adherent neurogenic cultures derived from postnatal or adult periventricular tissue contained subpopulations of GFAP-expressing cells that co-expressed nestin and LeX/CD15, two molecules associated with NSCs. In contrast, GFAP-expressing cells in similar cultures prepared from adult cerebral cortex did not express detectable levels of LeX/CD15, and exhibited no neurogenic potential. Fluorescence-activated cell sorting (FACS) of both primary astrocyte cultures and adherent neurogenic cultures for LeX/CD15 showed that GFAP-expressing cells competent to act as multipotent NSCs were concentrated in the LeX-positive fraction. Using neurosphere assays and a transgenic ablation strategy, we confirmed that the predominant NSCs in primary astrocyte and adherent neurogenic cultures were GFAP-expressing cells. These findings demonstrate that GFAP-expressing cells derived from postnatal and adult forebrain are heterogeneous in both molecular phenotype and neurogenic potential in vitro, and that this heterogeneity exists before exposure to neurogenic conditions. The findings provide evidence that GFAP-expressing NSCs are phenotypically and functionally distinct from non-neurogenic astrocytes.

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Glial Fibrillary Acidic Protein (GFAP)-like Immunoreactivity in Rat Endocrine Pancreas

Cited by 17 publications

References 47 publications

Characterization of pancreatic glucagon-producing tumors and pituitary gland tumors in transgenic mice overexpressingMYCNinhGFAP-positive cells

Characterization of pancreatic glucagon-producing tumors and pituitary gland tumors in transgenic mice overexpressingMYCNinhGFAP-positive cells

Identification and characterization of a novel isoform of the vesicular γ-aminobutyric acid transporter with glucose-regulated expression in rat islets

Phenotypic and functional heterogeneity of GFAP‐expressing cells in vitro: Differential expression of LeX/CD15 by GFAP‐expressing multipotent neural stem cells and non‐neurogenic astrocytes

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