Expression of nerve growth factor and its high-affinity receptor Trk-A in the rat pancreas during embryonic and fetal life

Miralles, Francisco; Philippe, P.; Czernichow, P; Scharfmann, Raphaël

doi:10.1677/joe.0.1560431

Cited by 40 publications

(27 citation statements)

References 32 publications

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“…Nestin may be a marker of pancreatic stem cells. Ngfa, Ngfg, and Mgat1 are also expressed in the developing pancreas and may participate in morphogenesis (20,26,30,40). Sel1h downregulates the Notch system, which is involved in regulating the balance between cell differentiation and stem cell proliferation (5).…”

Section: Discussionmentioning

confidence: 99%

Progression or Resolution of Coxsackievirus B4-Induced Pancreatitis: a Genomic Analysis

Ostrowski¹,

Reilly

Collins

et al. 2004

J Virol

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Group B coxsackieviruses are associated with chronic inflammatory diseases of the pancreas, heart, and central nervous system. Chronic pancreatitis, which can develop from acute pancreatitis, is considered a premalignant disorder because it is a major risk factor for pancreatic cancer. To explore the genetic events underlying the progression of acute to chronic disease, a comparative analysis of global gene expression during coxsackievirus B4-induced acute and chronic pancreatitis was undertaken. A key feature of acute pancreatitis that resolved was tissue regeneration, which was accompanied by increased expression of genes involved in cell growth, inhibition of apoptosis, and embryogenesis and by increased division of acinar cells. Acute pancreatitis that progressed to chronic pancreatitis was characterized by lack of tissue repair, and the expression map highlighted genes involved in apoptosis, acinoductular metaplasia, remodeling of the extracellular matrix, and fibrosis. Furthermore, immune responses appeared skewed toward development of alternatively activated (M2) macrophages and T helper 2 (Th2) cells during disease that resolved and toward classically activated (M1) macrophages and Th1 cells during disease that progressed. Our hypothesis is that growth and differentiation signals coupled with the M2/Th2 milieu favor acinar cell proliferation, while diminished growth signals and the M1/Th1 milieu favor apoptosis of acinar cells and remodeling/proliferation of the extracellular matrix, resulting in fibrosis.The group B coxsackieviruses are associated with chronic inflammatory diseases of the pancreas (insulin-dependent diabetes mellitus and idiopathic chronic pancreatitis), heart (dilated cardiomyopathy), and central nervous system (12). Efforts to elucidate the mechanisms by which these viruses cause disease have focused on identifying the molecular determinants of viral virulence and understanding the immune response to infection. The molecular determinants of viral virulence for the group B coxsackieviruses are distinct, suggesting that these viruses induce disease via diverse mechanisms. For coxsackievirus B3 (CVB3), determinants of attenuation and virulence have been identified in the 5Ј untranslated region (42) and in VP2 (21). For CVB4, Thr-129 of VP1 is a major determinant of virulence (11). The precise mechanism by which the viral molecular determinants cause tissue injury is not clear. During coxsackievirus B infection, both virus-induced cytopathology and immunopathological mechanisms have been implicated in mediating tissue injury (12, 36).Our mouse model uses two serologically indistinguishable variants of the CVB4 serotype that cause acute and chronic pancreatitis reminiscent of clinical disease. The CVB4-P variant induces a transient, acute disease which shares pathological features (edema and inflammation) (34) with acute, interstitial pancreatitis in humans (9). The CVB4-V variant induces a severe, acute disease which progresses to chronic pancreatitis. CVB4-V-induced chronic pancreatitis ...

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Section: Discussionmentioning

confidence: 99%

Progression or Resolution of Coxsackievirus B4-Induced Pancreatitis: a Genomic Analysis

Ostrowski¹,

Reilly

Collins

et al. 2004

J Virol

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“…NGF mRNA and protein expression have been observed in rat islets but the cell type expressing the neurotrophin has not been characterized [16,52,53]. A recent study showed that rat beta cells produce NGF [54] whereas previous reports failed to demonstrate NGF mRNA and/or receptor expression [17±19,55].…”

Section: Discussionmentioning

confidence: 99%

NGF-withdrawal induces apoptosis in pancreatic beta cells in vitro

et al. 2001

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Beta cells originate from precursor cells in the pancreatic ducts, although the possibility of an early migration of the neuroectodermal cells to the endoderm has not been completely ruled out [1±3]. These cells share many similarities with neurons such as the expression of neuron-specific molecules, that is tyrosine hydroxylase or dopamine b-hydroxylase. They are electrically excitable like neurons and insulin release is a process resembling neurotransmitter release, involving cell depolarization and vesicle exocytosis [4]. Beta cells and neuronal cells could be sensitive to the same growth and differentiation factors since specific transcriptional activators (Islets1, Pax-6 and Beta2) are expressed in beta cells and neurons, whereas the transcriptional repressor factor NRSF/ Diabetologia (2001) Abstract Aims/hypothesis. Using primary cultures of human pancreatic islets, purified human pancreatic beta cells and the mouse bTC6-F7 cell line, we analysed the expression of nerve growth factor, (NGF/NGF) receptors in beta cells. To investigate whether NGF could sub-serve an autocrine antiapoptotic role in beta cells, we studied the effects of NGF withdrawal using a neutralizing monoclonal anti-NGF antibody.Methods. The expression of NGF and NGF receptors (gp140 Trk-A and p75 NTR ) were analysed by RT-PCR and immunofluorescence. Pulse-chase experiments and beta cell/PC12 co-cultures were used to investigate NGF production and secretion from beta cells. Possible apoptosis induced by NGF withdrawal was monitored by phosphatidylserine translocation, nucleosomal formation, DNA laddering and FACS analysis. Involvement of transcription/translation mechanisms were investigated as well as the gp140Trk-A required. Finally, signal transduction pathways typically involved in apoptotic mechanisms were analysed by western blot analysis.Results. We show that NGF and both NGF receptors, gp140Trk-A and p75 NTR are expressed in beta cells where NGF is produced and secreted in a biologically active form. NGF-withdrawal induces beta-cell transcription/translation independent apoptosis but mediated by gp140Trk-A. Analysis of signal transduction pathways revealed that NGF withdrawal inhibits the PI3-K, protein kinase B (AKT), Bad survival pathway and activates c-Jun kinase (JNK) whereas ERKs and p38 mitogen-activated protein kinase (MAPK) are not affected. Moreover, Bcl-XL, but not Bcl-2 protein expression are reduced. Conclusion/interpretaiton. We suggest that the integrity of the NGF/NGF receptor system and NGF bioavailability participate in controlling beta-cell survival in culture which represents a key issue for improving possibilities for transplantations in the treatment of diabetes. [Diabetologia (2001

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“…Nevertheless, the role of neurotrophins on gut endocrine cells, at least in teleosts, is unknown, and presumably it would not differ from the classic neurotrophic-neurotropic role. Rather in this case neurotrophins could regulate the synthesis of hormones and peptides (Kanaka-Gantenbein et al, 1995;(Varilek et al, 1995) Scharfmann, 1997;Miralles et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, co-localization or co-expression of neurotrophin receptors and neuropeptides/ hormones has been observed in non-neuronal cells such as the endocrine cells of the pancreas (Kanaka-Gantenbein et al, 1995;Miralles et al, 1998). Moreover, in mammals and birds some gut endocrine cells, recognized by use of general markers, express immunoreactivity (IR) for Trk neurotrophin receptor proteins (Esteban et al, 1995;Shibayama and Koizumi, 1996).…”

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confidence: 99%

Co-localization of Trk neurotrophin receptors and regulatory peptides in the endocrine cells of the teleostean stomach

et al. 1999

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Recently it has been observed that a subpopulation of gut endocrine cells in vertebrates express Trk-like proteins, suggesting that neurotrophins could regulate the synthesis and storage of amines and peptides of these cells. Nevertheless, the peptides and amines present in the endocrine cells that express Trks have not been characterized. In this study we used immunohistochemistry to investigate the occurrence of Trk-like proteins (TrkA-like, TrkB-like and TrkC-like) and the possible co-localization of these with peptides and/or biogenic amines in the endocrine cells of the stomach of three teleost (bass, gilt-head and scorpionfish). No TrkA-like immunoreactivity (IR) was detected in the stomach of these species, whereas TrkB-like IR and TrkC-like IR were observed in numerous cells of the gastric epithelium. TrkB-like immunoreactive cells were present in all three species examined, and were particularly abundant in the blind sac. Conversely, TrkC-like immunoreactive cells were found only in the bass stomach, apparently co-localized with TrkB-like IR. TrkB-like IR was found co-localized with somatostatin IR in scorpionfish, and with somatostatin and CGRP IR in gilt-head and bass. Gastric endocrine cells expressing 5-HT, glucagon, insulin, met-, leu-enkephalin, substance P, PYY, VIP, CCK, NPY, bombesin and motilin were unreactive for Trk-like proteins. The present results provide direct evidence for the occurrence of Trk-like neurotrophin receptor proteins in a subpopulation of the teleostean gastric endocrine cells and suggest that neurotrophins could regulate, as in neurons, the expression of some neuropeptides such as somatostatin and CGRP. Anat Rec 256: [219][220][221][222][223][224][225][226] 1999.

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Expression of nerve growth factor and its high-affinity receptor Trk-A in the rat pancreas during embryonic and fetal life

Cited by 40 publications

References 32 publications

Progression or Resolution of Coxsackievirus B4-Induced Pancreatitis: a Genomic Analysis

Progression or Resolution of Coxsackievirus B4-Induced Pancreatitis: a Genomic Analysis

NGF-withdrawal induces apoptosis in pancreatic beta cells in vitro

Co-localization of Trk neurotrophin receptors and regulatory peptides in the endocrine cells of the teleostean stomach

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