Role of ERK 1/2
Regulation of vitamin D receptor expression via estrogen-induced activation of the ERK 1/2 signaling pathway in colon and breast cancer cells 2005
Differential Activation Mechanisms of Erk-1/2 and p70S6K by Glucose in Pancreatic ß-Cells 2005
Xenoestrogen-Induced ERK-1 and ERK-2 Activation via Multiple Membrane-Initiated Signaling Pathways 2004
Relaxin, a Pregnancy Hormone, Is a Functional Endothelin-1 Antagonist 2003
Extracellular inosine modulates ERK 1/2 and p38 phosphorylation in cultured Sertoli cells: Possible participation in TNF-alpha modulation of ERK 1/2 2005
The Role of cAMP-dependent Signaling in Receptor-recognized Forms of alpha 2-Macroglobulin-induced Cellular Proliferation 2002
Genistein, a soy isoflavone, up-regulates expression of antioxidant genes: involvement of estrogen receptors, ERK1/2, and NF{kappa}B 2006
Role of TGF beta
Google Textbook The Skeleton : Biochemical, Genetic, and Molecular Interactions in Development and Homeostasis by Massaro, Edward J.
Positive and Negative Modulation of Vitamin D Receptor Function by Transforming Growth Factor-beta Signaling through Smad Proteins 1999
Cross-talk between 1,25-Dihydroxyvitamin D3 and Transforming Growth Factor-beta Signaling Requires Binding of VDR and Smad3 Proteins to Their Cognate DNA Recognition Elements 2001
VDR and SMAD pathway
Molecules involved
Papers VDR IL-6
RNA activation
PLoS One. 2010 Jan 22;5(1):e8848.
RNAa is conserved in mammalian cells.
Huang V, Qin Y, Wang J, Wang X, Place RF, Lin G, Lue TF, Li LC.
Helen-Diller Comprehensive Cancer Center, University of California San Francisco, San Francisco, California, USA.
Abstract
BACKGROUND: RNA activation (RNAa) is a newly discovered mechanism of gene activation triggered by small double-stranded RNAs termed 'small activating RNAs' (saRNAs). Thus far, RNAa has only been demonstrated in human cells and is unclear whether it is conserved in other mammals. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, we evaluated RNAa in cells derived from four mammalian species including nonhuman primates (African green monkey and chimpanzee), mouse, and rat. Previously, we identified saRNAs leading to the activation of E-cadherin, p21, and VEGF in human cells. As the targeted sequences are highly conserved in primates, transfection of each human saRNA into African green monkey (COS1) and chimpanzee (WES) cells also resulted in induction of the intended gene. Additional saRNAs targeting clinically relevant genes including p53, PAR4, WT1, RB1, p27, NKX3-1, VDR, IL2, and pS2 were also designed and transfected into COS1 and WES cells. Of the nine genes, p53, PAR4, WT1, and NKX3-1 were induced by their corresponding saRNAs. We further extended our analysis of RNAa into rodent cell types. We identified two saRNAs that induced the expression of mouse Cyclin B1 in NIH/3T3 and TRAMP C1 cells, which led to increased phosphorylation of histone H3, a downstream marker for chromosome condensation and entry into mitosis. We also identified two saRNAs that activated the expression of CXCR4 in primary rat adipose-derived stem cells. CONCLUSIONS/SIGNIFICANCE: This study demonstrates that RNAa exists in mammalian species other than human. Our findings also suggest that nonhuman primate disease models may have clinical applicability for validating RNAa-based drugs.
UCP and VDR
Am J Physiol Endocrinol Metab. 2009 Apr;296(4):E820-8. Epub 2009 Jan 27.
Involvement of the vitamin D receptor in energy metabolism: regulation of uncoupling proteins.
Wong KE, Szeto FL, Zhang W, Ye H, Kong J, Zhang Z, Sun XJ, Li YC.
Department of Medicine, Committee on Molecular Metabolism and Nutrition, The University of Chicago, MC 4076, 5841 S. Maryland Ave., Chicago, IL 60637, USA.
Abstract
Recent studies have established that vitamin D plays multiple biological roles beyond calcium metabolism; however, whether vitamin D is involved in energy metabolism is unknown. To address this question, we characterized the metabolic phenotypes of vitamin D receptor (VDR)-null mutant mice. Under a normocalcemic condition, VDR-null mice displayed less body fat mass and lower plasma triglyceride and cholesterol levels compared with wild-type (WT) mice; when placed on a high-fat diet, VDR-null mice showed a slower growth rate and accumulated less fat mass globally than WT mice, even though their food intake and intestinal lipid transport capacity were the same as WT mice. Consistent with the lower adipose mass, plasma leptin levels were lower and white adipocytes were histologically smaller in VDR-null mice than WT mice. The rate of fatty acid beta-oxidation in the white adipose tissue was higher, and the expression of uncoupling protein (UCP) 1, UCP2 and UCP3 was markedly upregulated in VDR-null mice, suggesting a higher energy expenditure in the mutant mice. Experiments using primary brown fat culture confirmed that 1,25-dihydroxyvitamin D3 directly suppressed the expression of the UCPs. Consistently, the energy expenditure, oxygen consumption, and CO2 production in VDR-null mice were markedly higher than in WT mice. These data indicate that vitamin D is involved in energy metabolism and adipocyte biology in vivo in part through regulation of beta-oxidation and UCP expression.
Iron and VDR
Papers VDR and iron
J Exp Med. 2010 Apr 12;207(4):731-50. Epub 2010 Apr 5.
Targeting iron homeostasis induces cellular differentiation and synergizes with differentiating agents in acute myeloid leukemia.
Fulltext
"Local Fulltext":
Callens C, Coulon S, Naudin J, Radford-Weiss I, Boissel N, Raffoux E, Wang PH, Agarwal S, Tamouza H, Paubelle E, Asnafi V, Ribeil JA, Dessen P, Canioni D, Chandesris O, Rubio MT, Beaumont C, Benhamou M, Dombret H, Macintyre E, Monteiro RC, Moura IC, Hermine O.
Centre National de la Recherche Scientifique UMR 8147, Paris 75015, France.
Comment in:
J Exp Med. 2010 Apr 12;207(4):677-80.
Abstract
Differentiating agents have been proposed to overcome the impaired cellular differentiation in acute myeloid leukemia (AML). However, only the combinations of all-trans retinoic acid or arsenic trioxide with chemotherapy have been successful, and only in treating acute promyelocytic leukemia (also called AML3). We show that iron homeostasis is an effective target in the treatment of AML. Iron chelating therapy induces the differentiation of leukemia blasts and normal bone marrow precursors into monocytes/macrophages in a manner involving modulation of reactive oxygen species expression and the activation of mitogen-activated protein kinases (MAPKs). 30% of the genes most strongly induced by iron deprivation are also targeted by vitamin D3 (VD), a well known differentiating agent. Iron chelating agents induce expression and phosphorylation of the VD receptor (VDR), and iron deprivation and VD act synergistically. VD magnifies activation of MAPK JNK and the induction of VDR target genes. When used to treat one AML patient refractory to chemotherapy, the combination of iron-chelating agents and VD resulted in reversal of pancytopenia and in blast differentiation. We propose that iron availability modulates myeloid cell commitment and that targeting this cellular differentiation pathway together with conventional differentiating agents provides new therapeutic modalities for AML.
Adipocytes and VDR
Papers VDR adipocytes
Biochem Biophys Res Commun. 1999 Jan 19;254(2):299-305.
Identification of inducible genes at the early stage of adipocyte differentiation of 3T3-L1 cells.
Imagawa M, Tsuchiya T, Nishihara T.
Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-Oka, Osaka, Suita, 565-0871, Japan. imagawa@phs.osaka-u.ac.jp
Abstract
Adipocyte differentiation takes place via a complex series of steps. While PPARgamma2 and C/EBPalpha are known to be master regulators, the events at the earliest stage of adipocyte differentiation are not yet known. In this study, we cloned the genes which are induced at the beginning of differentiation of 3T3-L1 preadipocyte cells. Of 58 clones obtained, only a few were already reported as the genes that are expressed differentially during adipocyte development. More than 30 clones are known but have been newly identified here as differentially expressed genes. Nineteen clones seemed to be unknown genes. The expression of RGS2, HSP105, Rho (TC10), VDR, and HIF-1alpha genes isolated here rapidly increased after the addition of inducers, and after 3-12 h the levels of expression decreased. The expression patterns of these mRNAs were different among growth-arrested and proliferating 3T3-L1 cells and NIH-3T3 cells, strongly indicating that some of the proteins identified here have crucial roles in the program of adipocyte differentiation.
The real inducer is IBMX that induces both HIF and VDR, that is very high in adipocytes
Induction of Bach1 and ARA70 gene expression at an early stage of adipocyte differentiation of mouse 3T3-L1 cells. 2002
sono le condizioni di carenza di ferro che li inducono come il VDR
ARA70-NCOA4
Activation of androgen receptor-associated protein 70 (ARA70) mRNA expression in ovarian cancer [5].
Bach1
Expression of HO-1 was also reduced in human cells when exposed to interferon-gamma or an iron chelator desferrioxamine, each of which induced Bach1 expression [3].
Hypoxia and VEGF
Papers VDR VEGF
Papers VEGF platelets
Flavonoids and VDR
Papers VDR flavonoids
Phytochemicals and regulation of the adipocyte life cycle.
J Nutr Biochem. 2008 Nov;19(11):717-26. Epub 2008 May 20.
Rayalam S, Della-Fera MA, Baile CA.
Natural products have potential for inducing apoptosis, inhibiting adipogenesis and stimulating lipolysis in adipocytes. The objective of this review is to discuss the adipocyte life cycle and various dietary bioactives that target different stages of adipocyte life cycle. Different stages of adipocyte development include preadipocytes, maturing preadipocytes and mature adipocytes. Various dietary bioactives like genistein, conjugated linoleic acid (CLA), docosahexaenoic acid, epigallocatechin gallate, quercetin, resveratrol and ajoene affect adipocytes during specific stages of development, resulting in either inhibition of adipogenesis or induction of apoptosis. Although numerous molecular targets that can be used for both treatment and prevention of obesity have been identified, targeted monotherapy has resulted in lack of success. Thus, targeting several signal transduction pathways simultaneously with multiple natural products to achieve additive or synergistic effects might be an appropriate approach to address obesity. We have previously reported two such combinations, namely, ajoene+CLA and vitamin D+genistein. CLA enhanced ajoene-induced apoptosis in mature 3T3-L1 adipocytes by synergistically increasing the expression of several proapoptotic factors. Similarly, genistein potentiated vitamin D's inhibition of adipogenesis and induction of apoptosis in maturing preadipocytes by an enhanced expression of VDR (vitamin D receptor) protein. These two examples indicate that combination therapy employing compounds that target different stages of the adipocyte life cycle might prove beneficial for decreasing adipose tissue volume by inducing apoptosis or by inhibiting adipogenesis or both.
