RGD Reference Report - Bile-acid-activated farnesoid X receptor regulates hydrogen sulfide production and hepatic microcirculation. - Rat Genome Database

Send us a Message



Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   

Bile-acid-activated farnesoid X receptor regulates hydrogen sulfide production and hepatic microcirculation.

Authors: Renga, Barbara  Mencarelli, Andrea  Migliorati, Marco  Distrutti, Eleonora  Fiorucci, Stefano 
Citation: Renga B, etal., World J Gastroenterol. 2009 May 7;15(17):2097-108. doi: 10.3748/wjg.15.2097.
RGD ID: 15042868
Pubmed: PMID:19418582   (View Abstract at PubMed)
PMCID: PMC2678580   (View Article at PubMed Central)
DOI: DOI:10.3748/wjg.15.2097   (Journal Full-text)


AIM: To investigate whether the farnesoid X receptor (FXR) regulates expression of liver cystathionase (CSE), a gene involved in hydrogen sulfide (H(2)S) generation.
METHODS: The regulation of CSE expression in response to FXR ligands was evaluated in HepG2 cells and in wild-type and FXR null mice treated with 6-ethyl chenodeoxycholic acid (6E-CDCA), a synthetic FXR ligand. The analysis demonstrated an FXR responsive element in the 5'-flanking region of the human CSE gene. The function of this site was investigated by luciferase reporter assays, chromatin immunoprecipitation and electrophoretic mobility shift assays. Livers obtained from rats treated with carbon tetrachloride alone, or in combination with 6-ethyl chenodeoxycholic acid, were studied for hydrogen sulphide generation and portal pressure measurement.
RESULTS: Liver expression of CSE is regulated by bile acids by means of an FXR-mediated mechanism. Western blotting, qualitative and quantitative polymerase chain reaction, as well as immunohistochemical analysis, showed that expression of CSE in HepG2 cells and in mice is induced by treatment with an FXR ligand. Administration of 6E-CDCA to carbon tetrachloride treated rats protected against the down-regulation of CSE expression, increased H(2)S generation, reduced portal pressure and attenuated the endothelial dysfunction of isolated and perfused cirrhotic rat livers.
CONCLUSION: These results demonstrate that CSE is an FXR-regulated gene and provide a new molecular explanation for the pathophysiology of portal hypertension.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
liver cirrhosis severityISONr1h4 (Mus musculus)15042868; 15042868mRNA:altered expression:liver (mouse)RGD 
liver cirrhosis severityIMP 15042868mRNA:altered expression:liver (mouse)RGD 
portal hypertension treatmentISONr1h4 (Rattus norvegicus)15042868; 15042868associated with liver cirrhosis and mRNA:altered expression:liver (rat)RGD 
portal hypertension treatmentIMP 15042868associated with liver cirrhosis and mRNA:altered expression:liver (rat)RGD 

Gene-Chemical Interaction Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
chenodeoxycholic acid multiple interactionsISOCth (Rattus norvegicus)15042868; 15042868chenodeoxycholic acid inhibits the reaction [Carbon Tetrachloride decreases expression and activity of cystathionine gamma-lyase in rat liver]RGD 
chenodeoxycholic acid multiple interactionsEXP 15042868chenodeoxycholic acid inhibits the reaction [Carbon Tetrachloride decreases expression and activity of cystathionine gamma-lyase in rat liver]RGD 
chenodeoxycholic acid multiple interactionsISONr1h4 (Rattus norvegicus)15042868; 15042868chenodeoxycholic acid inhibits the reaction [Carbon Tetrachloride decreases expression of Nr1h4 mRNA in rat liver], increases expression of Nr1H4 mRNA in rat liverRGD 
chenodeoxycholic acid multiple interactionsEXP 15042868chenodeoxycholic acid inhibits the reaction [Carbon Tetrachloride decreases expression of Nr1h4 mRNA in rat liver], increases expression of Nr1H4 mRNA in rat liverRGD 
tetrachloromethane decreases expressionISONr1h4 (Rattus norvegicus)15042868; 15042868Carbon Tetrachloride decreases expression of Nr1h4 mRNA in rat liverRGD 
tetrachloromethane decreases expressionEXP 15042868Carbon Tetrachloride decreases expression of Nr1h4 mRNA in rat liverRGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
response to norepinephrine  IMP 15042868 RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
liver fibrosis treatmentIMP 15042868mRNA:altered expression:liver ratRGD 
Objects Annotated

Genes (Rattus norvegicus)
Cth  (cystathionine gamma-lyase)
Nr1h4  (nuclear receptor subfamily 1, group H, member 4)

Genes (Mus musculus)
Cth  (cystathionine gamma lyase)
Nr1h4  (nuclear receptor subfamily 1, group H, member 4)

Genes (Homo sapiens)
CTH  (cystathionine gamma-lyase)
NR1H4  (nuclear receptor subfamily 1 group H member 4)


Additional Information