1.Action Mechanisms of Hormone Binding to Nuclear Receptors: Transcriptional Coregulators of the Nuclear Receptor Superfamily.
Jae Woon LEE ; Jae Hun CHEONG ; Young Chul LEE ; Soon Young NA ; Soo Kyung LEE
Journal of Korean Society of Endocrinology 2000;15(3):402-412
No Abstract Available.
Receptors, Cytoplasmic and Nuclear*
4.The relationship between bone-loss of steroid-induced osteonecrosis and local expression of OPG/OCIF.
Yan WANG ; Zhiyong CHI ; Gang HAN
Chinese Journal of Preventive Medicine 2002;36(7):534-537
OBJECTIVETo probe the relationship between the osteoprotegerin/osteoclastogenesis inhibitory factor (OPG/OCIF) expression of bone and the relative bone-loss.
METHODSSteroid-induced osteonecrosis-model was reproduced in thirty-one new Zealand hares, and 24 ones were alive 3 days after administration of endotoxin and methylprednisolone. The alive creatures were divided into control group and trial groups randomly. After the creatures being executed, bone-density measurement of the femurs, HE staining, Ca(+ +) staining and OPG/OCIF immunohistochemistry staining were performed, followed by image processing and statistical analysis.
RESULTSIn the early period of steroid-induced osteonecrosis, the local OPG/OCIF expression significantly decreased, with a large number of osteoclasts in the local medulla, followed by a progressively bone-loss.
CONCLUSIONCorticosteroid could inhibit OPG/OCIF expression in the bone, increase the activity and differentiation of osteoclast relatively, and worsen bone-loss in steroid-induced osteonecrosis.
Bone Density ; Glycoproteins ; Osteoclasts ; Osteonecrosis ; Receptors, Cytoplasmic and Nuclear ; Receptors, Tumor Necrosis Factor
5.The Hairless Gene: A Putative Navigator of Hair Follicle Development.
Jeong Ki KIM ; Bong Kyu KIM ; Jong Keun PARK ; Jee Hyun CHOI ; Sungjoo KIM YOON
Genomics & Informatics 2011;9(3):93-101
The Hairless (HR) gene regulates the expression of several target genes as a transcriptional corepressor of nuclear receptors. The hair follicle (HF), a small independent organ of the skin, resides in the epidermis and undergoes regenerative cycling for normal hair formation. HF development requires many genes and signaling pathways to function properly in time and space, one of them being the HR gene. Various mutations of the HR gene have been reported to cause the hair loss phenotype in rodents and humans. In recent studies, it has been suggested that the HR gene is a critical player in the regulation of the hair cycle and, thus, HF development. Furthermore, the HR gene is associated with the Wnt signaling pathway, which regulates roliferation and differentiation of cells and plays an essential role in hair and skin development. In this review, we summarize the mutations responsible for human hair disorders and discuss the roles of the HR gene in HF development.
Epidermis
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Hair
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Hair Follicle
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Humans
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Phenotype
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Receptors, Cytoplasmic and Nuclear
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Rodentia
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Skin
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Wnt Signaling Pathway
6.Effects of farnesoid X receptor on lipid metabolism in L02 cells.
Jiang-Long HONG ; Wei SHEN ; Ming-Jun BAI
Chinese Journal of Hepatology 2008;16(12):935-939
OBJECTIVETo investigate the effects of farnesoid X receptor (FXR) on lipid metabolism in human hepatic L02 cells.
METHODSA steatosis model and an intervention model were established by treating human hepatocyte line L02 cells with sodium oleate or sodium oleate and sodium chenodeoxycholate (a natural agonist of FXR) respectively. Non-treated L02 cells served as controls. At three time points of 24, 48 and 72 hours, the accumulation of lipid droplets in the hepatocytes was observed by optical microscopy after oil red O staining, and the the expression of FXR and SREBP-1c receptors was detected by RT-PCR and Western blot.
RESULTSCompared with the controls, expressions of FXR mRNA and protein were down-regulated gradually in the steatosis model at 24, 48 and 72 hours, FXR mRNA/beta-actin mRNA was 0.186+/-0.02, 0.182+/-0.028 and 0.181+/-0.022, FXR protein/beta-tubulin protein was 0.105+/-0.016, 0.103+/-0.012 and 0.103+/-0.018, F from 0.01 to 0.14; 24 h vs 48 h, 48 vs72 h: P more than 0.05. The expressions of SREBP-1c mRNA and protein were increased gradually. At 24, 48 and 72 hours, SREBP-1c mRNA/beta-actin mRNA was 0.495+/-0.062, 0.579+/-0.064 and 0.612+/-0.067, SREBP-1c protein/beta-tubulin protein was 0.394+/-0.044, 0.488+/-0.066 and 0.543+/-0.064, F from 0.80 to 4.66, 24 h vs 48 h, 48 vs 72 h: P less than 0.05. In the intervention model, expressions of FXR mRNA and protein were increased markedly compared with the steatosis model. At 24, 48 and 72 hours, FXR mRNA/beta-actin mRNA was 0.253+/-0.041, 0.298+/-0.042 and 0.334+/-0.051, and FXR protein/beta-tubulin protein was 0.221+/-0.022, 0.313+/-0.041 and 0.341+/-0.046, F from 6.41 to 50.93, intervention models vs steatosis models at the same time points: P less than 0.05-0.01. Expressions of SREBP-1 c mRNA and protein were significantly reduced. At 24, 48 and 72 hours, SREBP-1c mRNA/beta-actin mRNA was 0.296+/-0.038, 0.328+/-0.037 and 0.341+/-0.055, and FXR protein /beta-tubulin protein was 0.295+/-0.038, 0.334+/-0.047 and 0.355+/-0.054, F from 8.84 to 48.46; intervention models vs steatosis models at the same time point: P less than 0.01. Both in the steatosis model and the intervention model, content of TG and lipids accumulations were much more than those in the controls. Compared with the intervention model, levels of TG and lipids accumulation were markedly increased in the steatosis model at 24, 48, 72 hours. At 24, 48 and 72 hours, TG/cellular total protein in microg/mg was 173.0+/-20.5, 253.4+/-36.1 and 361.2+/-50.7 in the steatosis model, while in the intervention model the data was 84.1+/-17.2, 113.0+/-14.5 and 127.2+/-20.1, F from 38.70 to 268.13, intervention models vs steatosis models at the same time point: P less than 0.01.
CONCLUSIONExpression of FXR is closely associated with lipid homeostasis in hepatocytes. Up-regulation of the expression of FXR may improve lipidosis in L02 cells. Its possible mechanism involves reduction of SREBP-1c expression and lipogenesis in hepatocytes.
Cell Line ; Fatty Liver ; metabolism ; Hepatocytes ; cytology ; metabolism ; Humans ; Lipid Metabolism ; Receptors, Cytoplasmic and Nuclear ; Up-Regulation
7.Progress in the role of farnesoid X receptor in metabolic regulation and tumor cell proliferation.
Yang XIE ; Xue-Yan ZHOU ; Hai-Ping HAO ; Guang-Ji WANG
Acta Physiologica Sinica 2014;66(2):252-258
Farnesoid X receptor (FXR) is a ligand-activated transcriptional factor belonged to the superfamily of nuclear receptors. In the past decades, FXR has been found with important roles in the regulation of metabolic homeostasis of bile acids, cholesterol, lipids and carbohydrates. Recent studies further demonstrate the potential protective effect of FXR against metabolic diseases, such as hyperglycemia and hyperlipidemia, as well as inflammatory bowel diseases (IBD). In addition, FXR plays an essential role in liver regeneration, tumor cell proliferation and apoptosis. However, the role of FXR in the development of tumor is still obscure and even with discrepancy. This article reviews the function of FXR in metabolic regulation and recent progress in basic, clinical and pharmacological researches related to tumor cell proliferation involving FXR.
Cell Proliferation
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Homeostasis
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Humans
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Neoplasms
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metabolism
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Receptors, Cytoplasmic and Nuclear
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metabolism
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Transcription Factors
8.The role of nuclear receptor transcription factor NR2F6 in tumor.
Ling HUANG ; Jiahui LIU ; Yi ZHU ; Quan ZHOU ; Bin XIAO ; Zhaohui SUN ; Linhai LI
Chinese Journal of Biotechnology 2021;37(8):2595-2602
Nuclear receptor subfamily 2, group F, member 6 (NR2F6) is a member of orphan nuclear receptors, which is expressed in major tissues and organs of the human body, and plays an important role in the regulation of various biological functions and gene expressions. Recent studies have shown that the expression of NR2F6 was up-regulated in a variety of malignant tumors and showed significant correlations with cancer progression. These findings triggered the widespread interest in understanding the relationship between NR2F6 and cancer development and progression. In addition, the latest studies have underscored that NR2F6 was involved in enhancing antitumor immune responses that could serve as a potential target for immune regulation. This review summarizes the biological functions of NR2F6 and its role in tumors, with the aim to provide new insights into effective cancer therapies.
Gene Expression Regulation
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Humans
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Neoplasms/genetics*
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Receptors, Cytoplasmic and Nuclear/genetics*
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Repressor Proteins/genetics*
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Transcription Factors/genetics*
9.Nuclear receptors and renal water transport regulation.
Acta Physiologica Sinica 2018;70(6):630-638
The function of kidney is maintaining water balance of our body through regulation of urine concentration and dilution. The aquaporins are molecular basis of renal urine production and water transport, and their expression and membrane translocation are regulated delicately. Nuclear receptors are a superfamily of ligand-activated transcription factors consisting of 48 members in human. They widely participate in a variety of physiological and pathophysiological regulation including growth and development, glucose and lipid metabolism, inflammation, immunology by regulating target gene transcription and expression. Increasing evidence demonstrates that these receptors are involved in the regulation of aquaporins expression and membrane translocation in kidney, thereby playing a major role in water homeostasis. Here we review the role of nuclear receptors in regulating renal water transport.
Aquaporins
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physiology
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Biological Transport
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Homeostasis
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Humans
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Kidney
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physiology
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Receptors, Cytoplasmic and Nuclear
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physiology
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Water
10.Effect of geniposidic acid on hepato-enteric circulation in cholestasis rats through Sirt1-FXR signaling pathway.
Hao CHEN ; Jia LI ; Lei HU ; Wei ZHAO ; Hao YU ; Han-Zhen LIU ; Shi-Tang MA
China Journal of Chinese Materia Medica 2019;44(4):787-795
To investigate the effects of geniposidic acid( GPA) on hepato-enteric circulation in cholestasis rats,and to explore the mechanism based on the sirtuin 1( Sirt1)-farnesol X receptor( FXR) pathway,sixty SD rats were randomly divided into 6 groups:blank control group,ANIT model group,ursodeoxycholic acid group( 100 mg·kg~(-1)·d-1 UDCA),and GPA high,medium and low( 100,50 and 25 mg·kg~(-1)·d-1) dosage groups,10 rats in each group. Corresponding drugs were intragastrically( ig) administered for10 days. After administration on day 8,all rats except blank rats were administered with 65 mg·kg~(-1)α-naphthalene isothiocyanate( ANIT) once. After the last administration,the serum levels of alanine aminotransferase( ALT),glutamine oxalacetate aminotransferase( AST),gamma-glutamyltransferase( γ-GGT),alkaline phosphatase( ALP),total bilirubin( TB) and total bile acid( TBA)were measured,and the mRNA transcription levels of Sirt1,FXR,multidrug resistant associated protein 2( MRP2),bile salt export pump( BSEP),sodium taurocholate contractible polypeptide( NTCP) in liver and apical sodium bile acid transporter( ASBT),ileum bile acid binding protein( IBABP) in ileum were detected by reverse transcription-polymerase chain reaction( RT-PCR). The protein expression levels of Sirt1,FXR and NTCP were detected by Western blot; the expression of MRP2,BSEP in liver and ASBT,IBABP in ileum were determined by immunofluorescence three staining. Primary rat hepatocytes were cultured in vitro to investigate the inhibitory effect of GPA on a potent and selective Sirt1 inhibitor( EX 527),and the mRNA and protein expression levels of Sirt1 and FXR were detected by RT-PCR and Western blot. GPA significantly decreased the levels of ALT,AST,γ-GGT,ALP,TB,TBA in serum( P<0.01) and improved the pathological damage of liver tissues in ANIT-induced cholestasis rats; significantly increased the mRNA and protein expression levels of Sirt1,FXR,MRP2,BSEP,NTCP in liver and ASBT,IBABP in ileum( P< 0.01). In vitro primary hepatocytes experiment indicated that the gene and protein expression levels of FXR and Sirt1 were noticeably improved by GPA in primary hepatocytes inhibited by EX-527( P<0.01). It was found that the improvement of GPA was in a dose-dependent manner. GPA could improve bile acid hepatointestinal circulation and play a liver protection and cholagogu role in cholestasis rats induced by ANIT.The mechanism may be that GPA activated FXR by regulating Sirt1,a key regulator of oxidative stress injury,and then the activated FXR could regulate protein of bile acid hepato-enteric circulation.
Animals
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Cholestasis
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Iridoid Glucosides
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Liver
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Rats
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Rats, Sprague-Dawley
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Receptors, Cytoplasmic and Nuclear
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Signal Transduction
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Sirtuin 1