2020
Neutrophils interact with cholangiocytes to cause cholestatic changes in alcoholic hepatitis
Takeuchi M, Vidigal PT, Guerra MT, Hundt MA, Robert ME, Olave-Martinez M, Aoki S, Khamphaya T, Kersten R, Kruglov E, de la Rosa Rodriguez R, Banales JM, Nathanson MH, Weerachayaphorn J. Neutrophils interact with cholangiocytes to cause cholestatic changes in alcoholic hepatitis. Gut 2020, 70: 342-356. PMID: 33214166, PMCID: PMC7906004, DOI: 10.1136/gutjnl-2020-322540.Peer-Reviewed Original ResearchConceptsBile ductCholestatic changesLimited treatment optionsPresence of cholestasisAbility of neutrophilsLife-threatening diseaseNew therapeutic targetsHuman bile ductIntracellular calcium channelsAlcoholic hepatitisLiver biopsyControl neutrophilsPathological findingsHepatocellular damageHistological findingsTreatment optionsCell adhesion moleculeHistological parametersDisease altersITPR3 expressionTherapeutic targetAnimal modelsCalcium channelsNeutrophilsPatients
2019
Effects of Endotoxin on Type 3 Inositol 1,4,5‐Trisphosphate Receptor in Human Cholangiocytes
Franca A, Filho A, Guerra MT, Weerachayaphorn J, dos Santos M, Njei B, Robert M, Lima C, Vidigal P, Banales JM, Ananthanarayanan M, Leite MF, Nathanson MH. Effects of Endotoxin on Type 3 Inositol 1,4,5‐Trisphosphate Receptor in Human Cholangiocytes. Hepatology 2019, 69: 817-830. PMID: 30141207, PMCID: PMC6351171, DOI: 10.1002/hep.30228.Peer-Reviewed Original ResearchConceptsToll-like receptor 4Alcoholic hepatitisEffect of endotoxinBile duct cellsNF-κBInhibition of TLR4Human cholangiocytesStimulation of TLR4Duct cellsSevere alcoholic hepatitisCholestasis of sepsisForms of cholestasisNF-κB subunitsP65/p50Trisphosphate receptorReceptor 4Clinical conditionsBicarbonate secretionHepatocellular changesITPR3 expressionCholestasisType 3 inositolLPS receptorAgonist stimulusSepsis
2018
Nonalcoholic fatty liver disease impairs expression of the type II inositol 1,4,5‐trisphosphate receptor
Khamphaya T, Chukijrungroat N, Saengsirisuwan V, Mitchell‐Richards K, Robert ME, Mennone A, Ananthanarayanan M, Nathanson MH, Weerachayaphorn J. Nonalcoholic fatty liver disease impairs expression of the type II inositol 1,4,5‐trisphosphate receptor. Hepatology 2018, 67: 560-574. PMID: 29023819, PMCID: PMC5893412, DOI: 10.1002/hep.29588.Peer-Reviewed Original ResearchConceptsNonalcoholic fatty liver diseaseImpaired liver regenerationNonalcoholic steatohepatitisLiver regenerationHuh7 cellsLiver diseaseEffect of NAFLDPrevalent liver diseaseFatty liver diseaseC-JunHigh-fructose dietLiver biopsy specimensCell proliferationCalcium signalingHepG2 cellsLiver of ratsCell nuclear antigenCalcium release channelSimple steatosisLiver biopsyFatty liverTrisphosphate receptorBiopsy specimensRat modelType II inositol
2017
Type 2 inositol trisphosphate receptor gene expression in hepatocytes is regulated by cyclic AMP
Kruglov E, Ananthanarayanan M, Sousa P, Weerachayaphorn J, Guerra MT, Nathanson MH. Type 2 inositol trisphosphate receptor gene expression in hepatocytes is regulated by cyclic AMP. Biochemical And Biophysical Research Communications 2017, 486: 659-664. PMID: 28327356, PMCID: PMC5421629, DOI: 10.1016/j.bbrc.2017.03.086.Peer-Reviewed Original ResearchMeSH KeywordsAdenylyl CyclasesAnimalsBinding SitesColforsinCREB-Binding ProteinCyclic AMPDactinomycinFastingGene Expression RegulationHep G2 CellsHepatocytesHumansInositol 1,4,5-Trisphosphate ReceptorsMaleMutationPrimary Cell CulturePromoter Regions, GeneticProtein BindingRatsRats, Sprague-DawleyResponse ElementsRNA, MessengerSignal TransductionThionucleotidesConceptsPost-translational modificationsRecruitment of CREBAdenylyl cyclase 6Transcriptional regulationType 2 inositolGene expressionPromoter activityTrisphosphate receptorCyclase 6CRE elementTreatment of hepatocytesReceptor gene expressionAC isoformsCREBHormonal regulationProtein levelsIntracellular CaD. AnalysisPromoterRelease channelExpressionCyclic AMPIP3R2RegulationRat hepatocytes
2016
Effects of andrographolide on intrahepatic cholestasis induced by alpha-naphthylisothiocyanate in rats
Khamphaya T, Chansela P, Piyachaturawat P, Suksamrarn A, Nathanson MH, Weerachayaphorn J. Effects of andrographolide on intrahepatic cholestasis induced by alpha-naphthylisothiocyanate in rats. European Journal Of Pharmacology 2016, 789: 254-264. PMID: 27475677, PMCID: PMC10804355, DOI: 10.1016/j.ejphar.2016.07.032.Peer-Reviewed Original ResearchConceptsCholestatic liver diseaseLiver diseaseIntrahepatic cholestasisLiver injuryProtective effectHepatic stellate cell activationAcute intrahepatic cholestasisAlpha-smooth muscle actinCholestatic liver injuryBile duct proliferationSerum alanine aminotransferaseNF-κB expressionSingle intraperitoneal injectionEffects of andrographolidePromising therapeutic optionEffective therapeutic approachPotent protective propertiesNuclear factor kappaStellate cell activationANIT injectionDuct proliferationTherapeutic optionsHepatoprotective effectPeriductular fibrosisAlternative therapies
2013
Deleterious effect of oltipraz on extrahepatic cholestasis in bile duct-ligated mice
Weerachayaphorn J, Luo Y, Mennone A, Soroka CJ, Harry K, Boyer JL. Deleterious effect of oltipraz on extrahepatic cholestasis in bile duct-ligated mice. Journal Of Hepatology 2013, 60: 160-166. PMID: 23978715, PMCID: PMC4054607, DOI: 10.1016/j.jhep.2013.08.015.Peer-Reviewed Original ResearchConceptsBile duct ligationBDL miceLiver injuryControl miceBile duct-ligated miceBile flow rateBile duct obstructionHepato-protective effectsSmooth muscle actin expressionLiver function markersSevere liver damageBile acid-independent flowHigher bile flowMatrix metalloproteinases-9Hepatic stellate cellsCancer preventive agentsMuscle actin expressionPromising cancer-preventive agentBiliary pressureSerum aminotransferasesLiver histologyBDL groupPhase II detoxificationPortal fibroblastsProfibrogenic genes
2012
Nuclear factor-E2-related factor 2 is a major determinant of bile acid homeostasis in the liver and intestine
Weerachayaphorn J, Mennone A, Soroka CJ, Harry K, Hagey LR, Kensler TW, Boyer JL. Nuclear factor-E2-related factor 2 is a major determinant of bile acid homeostasis in the liver and intestine. AJP Gastrointestinal And Liver Physiology 2012, 302: g925-g936. PMID: 22345550, PMCID: PMC3362073, DOI: 10.1152/ajpgi.00263.2011.Peer-Reviewed Original ResearchConceptsBile duct ligationBile acid homeostasisBile acid synthesisBile acidsLiver injuryAcid homeostasisMRNA expressionWild-type control miceBile acid transporter expressionCYP3A11 mRNA expressionBile salt export pumpBiliary bile acidsDeletion of Nrf2Bile acid reabsorptionRole of Nrf2Factor 2Bile acid hydroxylationPregnane X receptorBDL miceExpression of regulatorsControl miceDuct ligationNrf2 resultsBile secretionHepatobiliary transporters