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المؤلفون: Ellen G. J. Ripmeester, Tim J. M. Welting, Guus G. H. van den Akker, Don A. M. Surtel, Jessica S. J. Steijns, Andy Cremers, Lodewijk W. van Rhijn, Marjolein M. J. Caron
المساهمون: Orthopedie, RS: CAPHRI - R3 - Functioning, Participating and Rehabilitation, MUMC+: MA Orthopedie (9), RS: CAPHRI School for Public Health and Primary Care, MUMC+: MA Orthopedie (3)
المصدر: PLOS ONE, 17(2):e0263430. Public Library of Science
PLoS ONE, Vol 17, Iss 2 (2022)مصطلحات موضوعية: Transcription, Genetic, Bone Morphogenetic Protein 7, Up-Regulation/drug effects, Core Binding Factor Alpha 1 Subunit, urologic and male genital diseases, Transcription, Genetic/drug effects, Cell Proliferation/drug effects, POLYMERASE-I TRANSCRIPTION, Ribosomal/genetics, ACTS, Promoter Regions, Genetic, PHOSPHORYLATION, Cells, Cultured, Multidisciplinary, Cultured, Homeodomain Proteins/physiology, Up-Regulation, Chondrocytes/drug effects, Chondrogenesis/drug effects, embryonic structures, Medicine, Chondrogenesis, Transcription, Protein Biosynthesis/drug effects, EXPRESSION, animal structures, Science, Cells, RUNX2, Transcription Factors/physiology, Core Binding Factor Alpha 1 Subunit/genetics, Promoter Regions, Chondrocytes, UBF, Humans, ARTICULAR CHONDROCYTES, Promoter Regions, Genetic/drug effects, Cell Proliferation, Homeodomain Proteins, Genetic/drug effects, GENE-TRANSCRIPTION, urogenital system, REPRESSION, DNA, RNA, Ribosomal/genetics, Bone Morphogenetic Protein 7/pharmacology, RNA, Ribosomal, Protein Biosynthesis, RNA, Transcription Factors
الوصف: BMP7 is a morphogen capable of counteracting the OA chondrocyte hypertrophic phenotype via NKX3-2. NKX3-2 represses expression of RUNX2, an important transcription factor for chondrocyte hypertrophy. Since RUNX2 has previously been described as an inhibitor for 47S pre-rRNA transcription, we hypothesized that BMP7 positively influences 47S pre-rRNA transcription through NKX3-2, resulting in increased protein translational capacity. Therefor SW1353 cells and human primary chondrocytes were exposed to BMP7 and rRNA (18S, 5.8S, 28S) expression was determined by RT-qPCR. NKX3-2 knockdown was achieved via transfection of a NKX3-2-specific siRNA duplex. Translational capacity was assessed by the SUNsET assay, and 47S pre-rRNA transcription was determined by transfection of a 47S gene promoter-reporter plasmid. BMP7 treatment increased protein translational capacity. This was associated by increased 18S and 5.8S rRNA and NKX3-2 mRNA expression, as well as increased 47S gene promotor activity. Knockdown of NKX3-2 led to increased expression of RUNX2, accompanied by decreased 47S gene promotor activity and rRNA expression, an effect BMP7 was unable to restore. Our data demonstrate that BMP7 positively influences protein translation capacity of SW1353 cells and chondrocytes. This is likely caused by an NKX3-2-dependent activation of 47S gene promotor activity. This finding connects morphogen-mediated changes in cellular differentiation to an aspect of ribosome biogenesis via key transcription factors central to determining the chondrocyte phenotype.
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2رسالة جامعية
المؤلفون: Holmberg, Johan
مصطلحات موضوعية: Forelimb -- abnormalities, Forelimb -- embryology, Homeodomain proteins -- genetics, Homeodomain proteins -- physiology, Transcription factors -- genetics, Transcription factors -- physiology
Degree: Diss. (sammanfattning) Lund : Lunds universitet, 2008
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3رسالة جامعية
المؤلفون: Svensson, Per
مصطلحات موضوعية: Gene expression regulation -- physiology, Homeodomain proteins -- physiology, Pancreas -- metabolism, Stem cells -- metabolism, Trans-activators -- physiology
Degree: Diss. (sammanfattning) Umeå : Umeå universitet, 2008
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4رسالة جامعية
المؤلفون: Vallstedt, Anna
مصطلحات موضوعية: Cell differentiation -- physiology, Homeodomain proteins -- physiology, Homeodomain proteins -- metabolism, Nerve tissue proteins -- physiology, Nerve tissue proteins -- metabolism, Neurons -- physiology, Neurons -- metabolism, Neuroglia -- physiology, Neuroglia -- metabolism, Transcription factors -- physiology, Transcription factors -- metabolism, Spinal cord -- cytology
URL الوصول: http://diss.kib.ki.se/2004/91-7140-132-6/
Degree: Diss. (sammanfattning) Stockholm : Karol. inst., 2004
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المؤلفون: Muriel Jaquet, Naoyuki Miura, Amélie Sabine, Damien Bebber, René Hägerling, Yan Agalarov, Anna Pfenniger, Tatiana V. Petrova, Brenda R. Kwak, Taija Makinen, Hélène Maby-El Hajjami, Ralf H. Adams, Cathrin Pollmann, Olivier Dormond, Friedemann Kiefer, J. M. Calmes
المصدر: Developmental cell
Developmental Cell, Vol. 22, No 2 (2012) pp. 430-45مصطلحات موضوعية: RNA, Messenger/genetics, ddc:616.07, Mechanotransduction, Cellular, Connexins, Mice, 0302 clinical medicine, Tumor Suppressor Proteins/physiology, Mechanotransduction, Lymphangiogenesis, Mechanotransduction, Cellular/physiology, Calcineurin/genetics/metabolism, Mice, Knockout, 0303 health sciences, biology, Calcineurin, Gene Expression Regulation, Developmental, Forkhead Transcription Factors/physiology, NFAT, Forkhead Transcription Factors, Homeodomain Proteins/physiology, Flow Cytometry, Cell biology, Endothelial stem cell, Lymphatic system, FOXC2, Signal Transduction, Blotting, Western, Morphogenesis, Connexins/genetics/metabolism, Real-Time Polymerase Chain Reaction, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, Animals, RNA, Messenger, Molecular Biology, Transcription factor, 030304 developmental biology, Cell Proliferation, Lymphatic Vessels, Homeodomain Proteins, Tumor Suppressor Proteins, Cell Biology, Embryo, Mammalian, Lymphangiogenesis/physiology, Lymphatic Vessels/cytology/metabolism, Immunology, biology.protein, Embryo, Mammalian/cytology/metabolism, 030217 neurology & neurosurgery, Developmental Biology
الوصف: SummaryLymphatic valves are essential for efficient lymphatic transport, but the mechanisms of early lymphatic-valve morphogenesis and the role of biomechanical forces are not well understood. We found that the transcription factors PROX1 and FOXC2, highly expressed from the onset of valve formation, mediate segregation of lymphatic-valve-forming cells and cell mechanosensory responses to shear stress in vitro. Mechanistically, PROX1, FOXC2, and flow coordinately control expression of the gap junction protein connexin37 and activation of calcineurin/NFAT signaling. Connexin37 and calcineurin are required for the assembly and delimitation of lymphatic valve territory during development and for its postnatal maintenance. We propose a model in which regionally increased levels/activation states of transcription factors cooperate with mechanotransduction to induce a discrete cell-signaling pattern and morphogenetic event, such as formation of lymphatic valves. Our results also provide molecular insights into the role of endothelial cell identity in the regulation of vascular mechanotransduction.Video Abstract
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المؤلفون: Haecker, Achim, Bergman, Mattias, Neupert, Christine, Moussian, Bernard, Luschnig, Stefan, Aebi, Markus, Mannervik, Mattias
المصدر: Development. 135(10):1745-9
مصطلحات موضوعية: Animals, Body Patterning/physiology, Drosophila Proteins/metabolism/*physiology, Drosophila melanogaster/*embryology/enzymology, Embryo, Nonmammalian/physiology, Endoplasmic Reticulum/metabolism, Eukaryotic Initiation Factor-2/metabolism, Gastrulation, Glucosyltransferases/genetics/*metabolism/physiology, Glycosylation, Homeodomain Proteins/physiology, Mutation, Phosphorylation, Signal Transduction, Transcription Factors/metabolism/physiology
وصف الملف: print
URL الوصول: https://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-15806
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Retrieve&list_uids=18403407&dopt=Citation -
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المؤلفون: Leanne Toube, Pedro Luis Herrera, Xunlei Zhou, Peter Gruss, Till Marquardt, Asher Berry, Ruth Ashery-Padan
المصدر: Developmental Biology, Vol. 269, No 2 (2004) pp. 479-488
Developmental Biologyمصطلحات موضوعية: endocrine system, medicine.medical_specialty, Monosaccharide Transport Proteins, PAX6 Transcription Factor, Enteroendocrine cell, Lineage tracing, Transcription Factors/physiology, Neogenesis, Mice, Cre/loxP, Internal medicine, Diabetes Mellitus, medicine, Animals, Paired Box Transcription Factors, Monosaccharide Transport Proteins/genetics, Eye Proteins, Pancreas, Molecular Biology, Transcription factor, Homeodomain Proteins, Neurons, ddc:616, Glucose Transporter Type 2, Recombination, Genetic, biology, Endocrine cells, Cell Biology, Zebrafish Proteins, biology.organism_classification, eye diseases, Pax6, Pancreas/ physiology, Repressor Proteins, Homeobox Protein Nkx-2.2, Endocrinology, medicine.anatomical_structure, Diabetes Mellitus/ etiology, Homeodomain Proteins/ physiology, PDX1, sense organs, PAX6, Beta cell, Neurons/physiology, Transcription Factors, Developmental Biology, Hormone
الوصف: Pax6 transcription factor is required for islet cell number, morphology, and hormone gene expression. The perinatal lethality of Pax6 null mutants has restricted investigation of the role of Pax6 in normal endocrine cell function. Therefore, we devised the conditional inactivation of Pax6 using the Pdx1 and Pax6 regulatory domains to activate Cre in cells of either the entire pancreatic bud or only in endocrine cell lineages, respectively. Mutant pups died few days after birth, suffering from an overt diabetic phenotype that includes hyperglycemia, hypoinsulinemia, weight loss, and ketosis, indicating an essential role for Pax6 in beta cell function. Glucose-transporter type-2 expression was downregulated, but expression of several transcription factors essential for endocrine development was maintained. Our findings support a role for Pax6 activity in maintaining normal beta cell function after birth, but not for beta cell neogenesis during late embryonic development and early postnatal stages.
وصف الملف: application/pdf
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8دورية أكاديميةCharacterization and regulation of the hb9/mnx1 beta-cell progenitor specific enhancer in zebrafish.
المؤلفون: Arkhipova, Valeriya, Wendik, Bjorn, Devos, Nathalie, Ek, Olivier, Peers, Bernard, Meyer, Dirk
المصدر: Developmental Biology, 365 (1), 290-302 (2012)
مصطلحات موضوعية: Animals, Animals, Genetically Modified, Basic Helix-Loop-Helix Transcription Factors/physiology, Cell Differentiation/physiology, Cell Lineage/physiology, Eye Proteins/physiology, Homeodomain Proteins/physiology, Insulin-Secreting Cells/cytology/physiology, Islets of Langerhans/cytology/embryology, Nerve Tissue Proteins/physiology, Paired Box Transcription Factors/physiology, Repressor Proteins/physiology, Signal Transduction, Stem Cells/physiology, Transcription Factors/physiology, Zebrafish/embryology, Zebrafish Proteins/physiology, Life sciences, Genetics & genetic processes, Sciences du vivant, Génétique & processus génétiques
الوصف: Differentiation of insulin producing beta-cells is a genetically well defined process that involves functions of various conserved transcription factors. Still, the transcriptional mechanisms underlying specification and determination of beta-cell fate are poorly defined. Here we provide the description of a beta-cell progenitor specific enhancer as a model to study initial steps of beta-cell differentiation. We show that evolutionary non-conserved upstream sequences of the zebrafish hb9 gene are required and sufficient for regulating expression in beta-cells prior to the onset of insulin expression. This enhancer contains binding sites for paired-box transcription factors and two E-boxes that in EMSA studies show interaction with Pax6b and NeuroD, respectively. We show that Pax6b is a potent activator of endodermal hb9 expression and that this activation depends on the beta-cell enhancer. Using genetic approaches we show that pax6b is crucial for maintenance but not induction of pancreatic hb9 transcription. As loss of Pax6b or Hb9 independently results in the loss of insulin expression, the data reveal a novel cross-talk between the two essential regulators of early beta-cell differentiation. While we find that the known pancreatic E-box binding proteins NeuroD and Ngn3 are not required for hb9 expression we also show that removal of both E-boxes selectively eliminates pancreatic specific reporter expression. The data provide evidence for an Ngn3 independent pathway of beta-cell specification that requires function of currently not specified E-box binding factors.
Relation: urn:issn:0012-1606; urn:issn:1095-564X
URL الوصول: https://orbi.uliege.be/handle/2268/163988
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المؤلفون: Jacques Philippe, Liora S. Katz, Yvan Gosmain, Eric Marthinet
المصدر: Molecular and Cellular Biology, Vol. 29, No 8 (2009) pp. 2322-2334
مصطلحات موضوعية: Transcriptional Activation, endocrine system, PAX6 Transcription Factor, Prohormone convertase, Proprotein convertase 2, Gene Expression Regulation/*physiology, Nerve Tissue Proteins, Biology, Proglucagon, Glucagon, Paired Box Transcription Factors/*physiology, Alpha cell, Cell Line, Transactivation, Neuroendocrine Secretory Protein 7B2, Molecular Chaperones/genetics/metabolism, Proto-Oncogene Proteins c-maf/genetics, Repressor Proteins/*physiology, Cricetinae, Basic Helix-Loop-Helix Transcription Factors, Nerve Tissue Proteins/genetics, Proprotein Convertase 2/*genetics, Animals, Paired Box Transcription Factors, Eye Proteins, Molecular Biology, Transcription factor, Proglucagon/metabolism, Regulation of gene expression, ddc:616, Homeodomain Proteins, Basic Helix-Loop-Helix Transcription Factors/genetics, Homeodomain Proteins/*physiology, Cell Biology, Articles, Molecular biology, eye diseases, Cell biology, Repressor Proteins, Glucagon/biosynthesis, Proprotein Convertase 2, Gene Expression Regulation, Proto-Oncogene Proteins c-maf, Neuroendocrine Secretory Protein 7B2/*genetics, Eye Proteins/*physiology, sense organs, Molecular Chaperones
الوصف: Pax6 is important in the development of the pancreas and was previously shown to regulate pancreatic endocrine differentiation, as well as the insulin, glucagon, and somatostatin genes. Prohormone convertase 2 (PC2) is the main processing enzyme in pancreatic alpha cells, where it processes proglucagon to produce glucagon under the spatial and temporal control of 7B2, which functions as a molecular chaperone. To investigate the role of Pax6 in glucagon biosynthesis, we studied potential target genes in InR1G9 alpha cells transfected with Pax6 small interfering RNA and in InR1G9 clones expressing a dominant-negative form of Pax6. We now report that Pax6 controls the expression of the PC2 and 7B2 genes. By binding and transactivation studies, we found that Pax6 indirectly regulates PC2 gene transcription through cMaf and Beta2/NeuroD1 while it activates the 7B2 gene both directly and indirectly through the same transcription factors, cMaf and Beta2/NeuroD1. We conclude that Pax6 is critical for glucagon biosynthesis and processing by directly and indirectly activating the glucagon gene through cMaf and Beta2/NeuroD1, as well as the PC2 and 7B2 genes.
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المؤلفون: Maedler, Kathrin, Schumann, Desiree, Schulthess, Fabienne, Oberholzer, José, Bosco, Domenico, Berney, Thierry, Donath, Marc Y
المصدر: Diabetes, Vol. 55, No 9 (2006) pp. 2455-62
مصطلحات موضوعية: Adult, Male, endocrine system, Fas Ligand Protein, ddc:617, Adolescent, Homeodomain Proteins/physiology, Middle Aged, Glucose/pharmacology, Membrane Glycoproteins/physiology, Aging/physiology, Rats, Rats, Sprague-Dawley, Apoptosis/drug effects/physiology, Insulin-Secreting Cells/cytology, Tumor Necrosis Factors/physiology, Animals, Humans, Trans-Activators/physiology, Antigens, CD95/physiology, Cells, Cultured, Aged, Cell Proliferation
الوصف: Type 2 diabetes is characterized by a deficit in beta-cell mass, and its incidence increases with age. Here, we analyzed beta-cell turnover in islets from 2- to 3- compared with 7- to 8-month-old rats and in human islets from 53 organ donors with ages ranging from 17 to 74 years. In cultured islets from 2- to 3-month-old rats, the age at which rats are usually investigated, increasing glucose from 5.5 to 11.1 mmol/l decreased beta-cell apoptosis, which was augmented when glucose was further increased to 33.3 mmol/l. In parallel, beta-cell proliferation was increased by both 11.1 and 33.3 mmol/l glucose compared with 5.5 mmol/l. In contrast, in islets from 7- to 8-month-old rats and from adult humans, increasing glucose concentrations from 5.5 to 33.3 mmol/l induced a linear increase in beta-cell death and a decrease in proliferation. Additionally, in cultivated human islets, age correlated positively with the sensitivity to glucose-induced beta-cell apoptosis and negatively to baseline proliferation. In rat islets, constitutive expression of Fas ligand and glucose-induced Fas receptor expression were observed only in 7- to 8-month-old but not in 2- to 3-month-old islets, whereas no age-dependent changes in the Fas/Fas ligand system could be detected in human islets. However, pancreatic duodenal homeobox (PDX)-1 expression decreased with age in pancreatic tissue sections of rats and humans. Furthermore, older rat islets were more sensitive to the high-glucose-mediated decrease in PDX-1 expression than younger islets. Therefore, differences in glucose sensitivity between human and 2- to 3-month-old rat islets may be due to both differences in age and in the genetic background. These data provide a possible explanation for the increased incidence of type 2 diabetes at an older age and support the use of islets from older rats as a more appropriate model to study glucose-induced beta-cell apoptosis.
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