Search results for "TRANSCRIPTION FACTOR"
showing 10 items of 1493 documents
Zoledronate, ibandronate and clodronate enhance osteoblast differentiation in a dose dependent manner – A quantitative in vitro gene expression analy…
2010
Bisphosphonates are widely used in the clinical treatment of bone diseases with increased bone resorption. In terms of side effects, they are known to be associated with osteonecrosis of the jaw (BONJ). There are two groups of bisphosphonates: the nitrogen-containing bisphosphonates, e.g. zoledronate and ibandronate, and the non-nitrogen-containing bisphosphonates, e.g. clodronate. Their impact on bone metabolism seems to differ. The objective of this study was to compare the osteogenic differentiation potency of these two pharmacologic groups. Human osteoblasts were stimulated with zoledronate and ibandronate at concentrations of 5×10(-5) M, 5×10(-6) M and 5×10(-7) M over the experimental …
Regulation of glomerular basement membrane collagen expression by LMX1B contributes to renal disease in nail patella syndrome.
2001
Basement membrane (BM) morphogenesis is critical for normal kidney function. Heterotrimeric type IV collagen, composed of different combinations of six alpha-chains (1-6), is a major matrix component of all BMs (ref. 2). Unlike in other BMs, glomerular BM (GBM) contains primarily the alpha 3(IV) and alpha 4(IV) chains, together with the alpha 5(IV) chain. A poorly understood, coordinated temporal and spatial switch in gene expression from ubiquitously expressed alpha 1(IV) and alpha 2(IV) collagen to the alpha 3(IV), alpha 4(IV) and alpha 5(IV) chains occurs during normal embryogenesis of GBM (ref. 4). Structural abnormalities of type IV collagen have been associated with diverse biological…
Stress hormones promote growth of B16-F10 melanoma metastases: an interleukin 6- and glutathione-dependent mechanism
2013
[EN] Background: Interleukin (IL)-6 (mainly of tumor origin) activates glutathione (GSH) release from hepatocytes and its interorgan transport to B16-F10 melanoma metastatic foci. We studied if this capacity to overproduce IL-6 is regulated by cancer cell-independent mechanisms. Methods: Murine B16-F10 melanoma cells were cultured, transfected with red fluorescent protein, injected i.v. into syngenic C57BL/6J mice to generate lung and liver metastases, and isolated from metastatic foci using high-performance cell sorting. Stress hormones and IL-6 levels were measured by ELISA, and CRH expression in the brain by in situ hybridization. DNA binding activity of NF-kappa B, CREB, AP-1, and NF-IL…
A common mechanism of action of the selective serotonin reuptake inhibitors citalopram and fluoxetine: Reversal of chronic psychosocial stress-induce…
2010
The transcription factor CREB regulates adaptive responses like memory consolidation, addiction, and synaptic refinement. Recently, chronic psychosocial stress as animal model of depression has been shown to stimulate CREB transcriptional activity in the brain; this stimulation was prevented by treatment with the antidepressant imipramine, which inhibits both noradrenaline and serotonin reuptake. However, it was unknown whether the selective inhibition of serotonin reuptake is sufficient for inhibition of stress-induced CREB activation, as it is for the clinical antidepressant effect. Therefore, the effect of two selective serotonin reuptake inhibitors (SSRIs), citalopram and fluoxetine, wa…
Sox17 regulates liver lipid metabolism and adaptation to fasting.
2014
Liver is a major regulator of lipid metabolism and adaptation to fasting, a process involving PPARalpha activation. We recently showed that the Vnn1 gene is a PPARalpha target gene in liver and that release of the Vanin-1 pantetheinase in serum is a biomarker of PPARalpha activation. Here we set up a screen to identify new regulators of adaptation to fasting using the serum Vanin-1 as a marker of PPARalpha activation. Mutagenized mice were screened for low serum Vanin-1 expression. Functional interactions with PPARalpha were investigated by combining transcriptomic, biochemical and metabolic approaches. We characterized a new mutant mouse in which hepatic and serum expression of Vanin-1 is …
Mutations in the NKX2.5 Gene and the PAX8 Promoter in a Girl with Thyroid Dysgenesis
2011
Screening of the known candidate genes involved in thyroid organogenesis has revealed mutations in a small subset of patients with congenital hypothyroidism due to thyroid dysgenesis (TD).We studied a girl with TD who had mutations in two transcription factors involved in thyroid development.Sequencing analysis of candidate genes involved in thyroid gland development revealed a new paternally inherited heterozygous mutation in the NKX2.5 gene (S265R) and a new maternally inherited heterozygous mutation in the PAX8 promoter region (-456CT). Both parents and a brother, who was also heterozygous for both mutations, were phenotypically normal. Immunofluorescence microscopy showed a correct nucl…
Transcription factors controlling development and function of innate lymphoid cells.
2014
Abstract Innate lymphoid cells (ILCs) are a heterogeneous group of lymphocytes, which play an important role in tissue homeostasis at epithelial surfaces. They are scarce in spleen and lymph nodes, but substantial numbers can be found in the intestinal mucosa even at steady state. There, they represent the first line of defence against invading pathogens and contribute to lymphorganogenesis, tissue repair and, when inappropriately activated, immune pathology. Lineage-specific development, function and maintenance of these cells depend on a restricted set of transcription factors that partially emerged as a result of diversification and selection during vertebrate evolution. The differential…
IL-27 controls the development of inducible regulatory T cells and Th17 cells via differential effects on STAT1
2007
IL-27 is an IL-12-related cytokine frequently present at sites of inflammation that can promote both anti- and pro-inflammatory immune responses. Here, we have analyzed the mechanisms how IL-27 may drive such divergent immune responses. While IL-27 suppressed the development of proinflammatory Th17 cells, a novel role for this cytokine in inhibiting the development of anti-inflammatory, inducible regulatory T cells (iTreg) was identified. In fact, IL-27 suppressed the development of adaptive, TGF-beta-induced Forkhead box transcription factor p3-positive (Foxp3(+)) Treg. Whereas the blockade of Th17 development was dependent on the transcription factor STAT1, the suppression of iTreg develo…
A MiR-142-3p/EGR2 Feedback Circuitry In Human CSF-1 Driven Differentiation of Monocytes Into Macrophages
2011
Abstract Abstract 2366 Colony-stimulating factor-1 (CSF-1 or M-CSF) triggers the differentiation of human peripheral blood monocytes into macrophages through and integrated cytokine/transcription factors circuitry. Using microarray profiling to explore the role of microRNAs (miRNAs) in this molecular circuitry, we identified the down-regulation of miR-142-3p in human macrophages obtained from CSF-1-treated monocytes. We show that miR-142-3p is a repressor of the transcription factor EGR2 (Early Growth Response 2) through direct 3'UTR interactions. Interestingly, EGR2 binds the promoter of the pre-miR-142-3p gene to negatively regulate its expression, identifying a self-regulatory feedback l…
Translation of HTT mRNA with expanded CAG repeats is regulated by the MID1-PP2A protein complex.
2012
Expansion of CAG repeats is a common feature of various neurodegenerative disorders, including Huntington's disease. Here we show that expanded CAG repeats bind to a translation regulatory protein complex containing MID1, protein phosphatase 2A and 40S ribosomal S6 kinase. Binding of the MID1-protein phosphatase 2A protein complex increases with CAG repeat size and stimulates translation of the CAG repeat expansion containing messenger RNA in a MID1-, protein phosphatase 2A- and mammalian target of rapamycin-dependent manner. Our data indicate that pathological CAG repeat expansions upregulate protein translation leading to an overproduction of aberrant protein and suggest that the MID1-com…