1.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
;
physiology
;
Biological Transport
;
Homeostasis
;
Humans
;
Kidney
;
physiology
;
Receptors, Cytoplasmic and Nuclear
;
physiology
;
Water
2.Role of PXR and CAR in Cholestasis.
The Korean Journal of Hepatology 2006;12(1):5-15
Cholestatic liver diseases are characterized by impairments of bile flows and accumulations of biliary constituents such as bile acids and bilirubin. The changes of phase I and II metabolism and the hepatobiliary transport system minimize cholestatic liver injury. These adaptive responses are transcriptionally regulated by several nuclear receptors. Recent studies have revealed that the pregnane X receptor (PXR) and the constitutive androstane receptor (CAR) are key nuclear receptors for regulating many of the adaptive responses noted in cholestasis. PXR and CAR coordinately regulate not only bile acid metabolism and transport, but also bilirubin clearance. PXR and CAR ligands may be useful in the future for the treatment of cholestatic liver disease.
Transcription Factors/metabolism/*physiology
;
Receptors, Steroid/metabolism/*physiology
;
Receptors, Cytoplasmic and Nuclear/metabolism/*physiology
;
Humans
;
Cholestasis/metabolism/*physiopathology
3.Regulation of bile acid metabolism-related signaling pathways by gut microbiota in diseases.
Er-Teng JIA ; Zhi-Yu LIU ; Min PAN ; Jia-Feng LU ; Qin-Yu GE
Journal of Zhejiang University. Science. B 2019;20(10):781-792
Over the past decade, there has been increasing attention on the interaction between microbiota and bile acid metabolism. Bile acids are not only involved in the metabolism of nutrients, but are also important in signal transduction for the regulation of host physiological activities. Microbial-regulated bile acid metabolism has been proven to affect many diseases, but there have not been many studies of disease regulation by microbial receptor signaling pathways. This review considers findings of recent research on the core roles of farnesoid X receptor (FXR), G protein-coupled bile acid receptor (TGR5), and vitamin D receptor (VDR) signaling pathways in microbial-host interactions in health and disease. Studying the relationship between these pathways can help us understand the pathogenesis of human diseases, and lead to new solutions for their treatments.
Bile Acids and Salts/metabolism*
;
Gastrointestinal Microbiome
;
Humans
;
Inflammation/metabolism*
;
Metabolic Syndrome/metabolism*
;
Receptors, Calcitriol/physiology*
;
Receptors, Cytoplasmic and Nuclear/physiology*
;
Receptors, G-Protein-Coupled/physiology*
;
Signal Transduction/physiology*
4.Liver X receptors and epididymal epithelium physiology.
Fabrice SAEZ ; Eléonore CHABORY ; Rémi CADET ; Patrick VERNET ; Silvère BARON ; Jean-Marc A LOBACCARO ; Joël R DREVET
Asian Journal of Andrology 2007;9(4):574-582
AIMTo investigate the roles of liver X receptors (LXR) in the lipid composition and gene expression regulation in the murine caput epididymidis. LXR are nuclear receptors for oxysterols, molecules derived from cholesterol metabolism that are present in mammals as two isoforms: LXRalpha, which is more specifically expressed in lipid-metabolising tissues, such as liver, adipose and steroidogenic tissues, and macrophages, whereas LXRbeta is ubiquitous. Their importance in reproductive physiology has been sustained by the fact that male mice in which the function of both LXR has been disrupted have fertility disturbances starting at the age of 5 months, leading to complete sterility by the age of 9 months. These defects are associated with epididymal epithelial degeneration in caput segments one and two, and with a sperm midpiece fragility, leading to the presence of isolated sperm heads and flagella when luminal contents are recovered from the cauda epididymidis.
METHODSThe lipid composition of the caput epididymidis of wild-type and LXR-deficient mice was assessed using oil red O staining on tissue cryosections and lipid extraction followed by high performance liquid chromatography or gas chromatography. Gene expression was checked by quantitative real time polymerase chain reaction.
RESULTSUsing LXR-deficient mice, we showed an alteration of the lipid composition of the caput epididymidis as well as a significantly decreased expression of the genes encoding SREBP1c, SCD1 and SCD2, involved in fatty acid metabolism.
CONCLUSIONAltogether, these results show that LXR are important regulators of epididymal function, and play a critical role in the lipid maturation processes occurring during sperm epididymal maturation.
Animals ; DNA Primers ; DNA-Binding Proteins ; deficiency ; genetics ; physiology ; Epididymis ; cytology ; physiology ; Epithelial Cells ; physiology ; Fatty Acids ; metabolism ; Homeostasis ; Lipids ; physiology ; Liver X Receptors ; Male ; Mice ; Mice, Knockout ; Orphan Nuclear Receptors ; Polymerase Chain Reaction ; Receptors, Cytoplasmic and Nuclear ; deficiency ; genetics ; physiology
5.PPAR gamma--the master of thrifty genes.
Acta Academiae Medicinae Sinicae 2002;24(3):315-320
Peroxisome proliferation is a cellular response to many chemical compounds affects including natural and modified fatty acids, phthalate and adipate ester plasticizers, leukotriene antagonists, acetylsalicylic acid and certain pathophysiological conditions including dramatic change of cellular morphology and enzymatic activity. Peroxisome proliferation phenomenon is seen primarily in liver and kidney. Hormones and nutritional factor can regulate peroxisome proliferation response. Sustained peroxisome proliferation can lead to hepatocarcinogenesis. The three types of peroxisome proliferator activated receptor, termed PPAR alpha, PPAR beta, and PPAR gamma, expressed in specific tissue, are consisted of a specific a nuclear receptor superfamily. After more than 10 years world wide research, the function of PPAR is clarified, as PPAR gamma, the master of thrifty genes, controls the expression of genes relative to adipogenesis, diabetes mellitus and obesity. The receptor is involved in transcriptional control of numerous cellular processes including cell cycle control, inflammation, immunoregulation and carcinogenesis.
Adipocytes
;
cytology
;
Animals
;
Cell Differentiation
;
Energy Metabolism
;
genetics
;
Humans
;
Intracellular Signaling Peptides and Proteins
;
Nuclear Receptor Coactivators
;
Peroxisome Proliferators
;
Receptors, Cytoplasmic and Nuclear
;
genetics
;
physiology
;
Transcription Factors
;
genetics
;
physiology
7.Development of selective androgen receptor modulators and their therapeutic applications.
Fang CHEN ; Gideon A RODAN ; Azi SCHMIDT
National Journal of Andrology 2002;8(3):162-168
Androgens control a broad range of physiological functions. The androgen receptor (AR), a steroid receptor that mediates the diverse biological actions of androgens, is a ligand inducible transcription factor. Abnormalities in the androgen signaling system result in many disturbances ranging from changes in gender determination and sexual development to psychiatric and emotional disorders. Androgen replacement therapy can improve many clinical conditions including hypogonadism and osteoporosis, but is limited by the lack of efficacious and safe therapeutic agents with easy delivery options. Recent progress in the area of gene regulation by steroid receptors and by selective receptor modulators provides an opportunity to examine if selective androgen receptor modulators (SARMs) could address some of the problems associated with current androgen therapy. Since the composition of the transcriptional initiation complex recruited by liganded AR determines the specificity of gene regulation, synthetic ligands aimed at initiating transcription of tissue and promoter specific genes offers hope for developing better androgen therapy. Establishment of assays that predict synthetic ligand activity is critical for SARM development. Advancement in high throughput compound screening and gene fingerprinting technologies, such as microarrays and proteomics, will facilitate and accelerate identification of effective SARMs.
Androgen Antagonists
;
pharmacology
;
Androgen Receptor Antagonists
;
Androgens
;
chemistry
;
metabolism
;
Chlormadinone Acetate
;
analogs & derivatives
;
pharmacology
;
Humans
;
Male
;
Receptors, Androgen
;
physiology
;
Receptors, Cytoplasmic and Nuclear
;
physiology
;
Testosterone Congeners
;
pharmacology
8.Nuclear transcription factors and lipid homeostasis in liver.
Ya-xi CHEN ; Ai-long HUANG ; Xiong-zhong RUAN
Chinese Medical Journal 2007;120(24):2290-2296
Animals
;
DNA-Binding Proteins
;
physiology
;
Homeostasis
;
Humans
;
Lipid Metabolism
;
Liver
;
metabolism
;
Liver X Receptors
;
NF-kappa B
;
physiology
;
Nuclear Proteins
;
physiology
;
Orphan Nuclear Receptors
;
Peroxisome Proliferator-Activated Receptors
;
physiology
;
Receptors, Cytoplasmic and Nuclear
;
physiology
;
Sterol Regulatory Element Binding Proteins
;
physiology
;
Transcription Factors
;
physiology
9.The role of peroxisome proliferators-activated receptor gamma (PPARgamma) during activation of hepatic stellate cells.
Wen-zhuo YANG ; Rui-lin LIU ; Min-de ZENG ; Lun-gen LU ; Xi-mei CHEN ; Shu-chang XU ; Yi-min MAO ; Zhu-ping FAN ; Zhi-rong WANG ; Ai-ping CAO
Chinese Journal of Hepatology 2004;12(4):216-218
OBJECTIVESTo observe the role of PPARgamma during the activation process of hepatic stellate cells (HSC).
METHODSBy morphology and RT-PCR, we study the changes of expression of PPARgamma in culture-activated HSC or in vivo activated HSC induced by dimethylnitrosamine (DMN).
RESULTSIn vitro, the expression level of PPARgamma in freshly isolated HSC (0.72+/-0.01) significantly reduced to 0.48+/-0.03 on the third day of culture (t = 19.8372, P<0.01), and reduced 70% on the seventh culture-day and could not be detected after the second passage. In vivo, HSC freshly isolated from normal control rats expressed PPARgamma (0.76+/-0.01). During the development of rat liver fibrosis induced by DMN, the expression level significantly reduced to 0.46+/-0.02 after the third injection of DMN (t = 29.5318, P<0.01), and reduced 66% on the end of first week and could not be detected on the end of second and third week.
CONCLUSIONThe expression of PPARgamma might play an important role on the maintenance of resting-form of HSC, and the reduction of expression of PPARgamma might be an early event during the activation process of HSC.
Animals ; Liver ; cytology ; Liver Cirrhosis ; etiology ; pathology ; Male ; RNA, Messenger ; analysis ; Rats ; Rats, Wistar ; Receptors, Cytoplasmic and Nuclear ; physiology ; Transcription Factors ; physiology
10.Farnesoid X receptor in the study of fibrosis and its treatments.
Cong ZHAO ; Yu-ling CONG ; Yi-jun XU ; Yan-ru YIN
Chinese Medical Journal 2013;126(19):3775-3781
Animals
;
Cholestasis
;
complications
;
Fibrosis
;
etiology
;
Gallbladder
;
pathology
;
Humans
;
Kidney
;
pathology
;
Lipid Metabolism
;
Liver Cirrhosis
;
etiology
;
therapy
;
Myocardium
;
pathology
;
Receptors, Cytoplasmic and Nuclear
;
physiology