No Abstract Available.
Receptors, Cytoplasmic and Nuclear*

No Abstract Available.
Receptors, Cytoplasmic and Nuclear* ; Receptors, Steroid*

Humans ; Liver Cirrhosis, Biliary ; Receptors, Cytoplasmic and Nuclear

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

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

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 ; Hair ; Hair Follicle ; Humans ; Phenotype ; Receptors, Cytoplasmic and Nuclear ; Rodentia ; Skin ; Wnt Signaling Pathway

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 ; Homeostasis ; Humans ; Neoplasms ; metabolism ; Receptors, Cytoplasmic and Nuclear ; metabolism ; Transcription Factors

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 ; physiology ; Biological Transport ; Homeostasis ; Humans ; Kidney ; physiology ; Receptors, Cytoplasmic and Nuclear ; physiology ; Water

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 ; Cholestasis ; Iridoid Glucosides ; Liver ; Rats ; Rats, Sprague-Dawley ; Receptors, Cytoplasmic and Nuclear ; Signal Transduction ; Sirtuin 1

To explore the effect of geniposidic acid (GPA) on the signal pathway of small heterodimer dimer receptor (SHP) and liver receptor homologue 1 (LRH-1) in cholestasis rats induced by alpha-naphthalene isothiocyanate (ANIT).
 Methods: Fifty SD rats were randomly divided into five groups: a blank group, an ANIT group, an ANIT+GPA (100 mg/kg) group, an ANIT+GPA (50 mg/kg) group, and an ANIT+GPA (25 mg/kg) group (n=10 in each group). The GPA were intragastrically given to rats for 10 days, and the control group and the ANIT group were given normal saline. At the eighth day of administration, all rats except the blank group were given 65 mg/kg ANIT once until the tenth day. After the last administration, serum total cholesterol (TC), triglyceride (TG) and total bile acids (TBA) were measured. The primary hepatocytes (RPH) were isolated from normal rats and cultured. The cells were divided into a blank group, an ANIT (40 μmol/L) group, an ANIT (40 μmol/L)+GPA (4.00 mmol/L) group (A4.00G group), an ANIT (40 μmol/L)+GPA (1.00 mmol/L) group (A1.00G group), and an ANIT (40 μmol/L)+GPA (0.25 mmol/L) group (A0.25G group). The mRNA transcription levels of SHP and cholesterol 7 alpha hydroxylase (CYP7A1) in RPH were detected by real-time-PCR, and the protein levels of SHP and CYP7a1 were detected by Western blotting. In the LRH-1 silence experiment, the RPH were divided into a blank group, a negative transfection group, a siRNA-LRH group (ZR group), a siRNA-LRH+GPA (4.00 mmol/L) group (ZR4.00G group), a siRNA-LRH+GPA (1.00 mmol/L) group (ZR1.00G group) and a siRNA-LRH+GPA (0.25 mmol/L) group (ZR0.25G group). The protein and mRNA levels of SHP, CYP7a1, LRH-1 were detected. In the over-expression experiment, the RPH were also divided into a blank group, a negative transfection group, a LRH-1 over-expression plasmid group (OE group), a LRH-1 over-expression plasmid+GPA (4.00 mmol/L) group (OE4.00G group), a LRH-1 over-expression plasmid+GPA (1.00 mmol/L) group (OE1.00G group), and a LRH-1 over-expression plasmid+GPA (0.25 mmol/L) group (OE0.25G group). The protein and mRNA levels of SHP, CYP7a1 and LRH-1 were detected.
 Results: Compared with the blank control group, TC and TBA were significantly increased (both P<0.01) in the ANIT group, but there was no difference in TG; compared with the ANIT group, the contents of TC and TBA in the AG100 and AG50 groups were significantly reduced (all P<0.01). Compared with the blank control group, the proteins and mRNA levels of SHP were significantly decreased (P<0.01), while CYP7a1 were dramatically increased (P<0.01) in the ANIT group; compared with the ANIT group, the proteins and mRNA levels of SHP in the A4.00G group and the A1.00G group were significantly increased (both P<0.01), while the levels of CYP7a1 proteins and mRNA levels were evidently decreased in the A4.00G and A1.00G groups (both P<0.01). Compared with the negative transfection group, the proteins and mRNA levels of CYP7a1 and LRH-1 were dramatically restrained (all P<0.01), while there was no change in SHP in the ZR group; compared with the ZR group, the proteins and mRNA levels of SHP were significantly increased (all P<0.01), while LRH-1 and CYP7a1 were not changed in the ZR4.00G, ZR1.00G and ZR0.25G groups. Compared with the negative transfection group, the protein and mRNA levels of CYP7a1 and LRH-1 were significantly suppressed in the OE group (all P<0.01). Compared with the OE group, the protein and mRNA levels of SHP were evidently increased in the OE4G and OE1G groups (all P<0.01), while LRH-1 and CYP7a1 were not changed in the OE4G, OE1G and OE0.25G groups.
 Conclusion: The over-expression of LRH-1 in RPH can up-regulate the mRNA and protein levels of CYP7a1. GPA can improve the biochemical and liver pathology of ANIT-induced cholestasis rats, which may be related to the decrease of CYP7a1 by activating SHP through LRH-1 in RPH.
Animals ; Cholestasis ; Iridoid Glucosides ; Rats ; Rats, Sprague-Dawley ; Receptors, Cytoplasmic and Nuclear ; Signal Transduction