TCDCA与TGR5相互作用的研究-豆柴文库

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TCDCA与TGR5相互作用的研究
Introduction
Bileacids(BAs)aremajorcomponentsofbile,whicharesynthesizedintheliverandsecretedintothesmallintestinetoaidinthedigestionandabsorptionofdietaryfats.Apartfromtheirimportantphysiologicalrole,BAsarealsoinvolvedinvariouspathologicalconditionssuchasliverdisease,diabetes,andcoloncancer.TwoimportantreceptorsthatinteractwithBAsaretaurocholicacidco-carryingmembranetransporter(TCDCA)andG-proteincoupledbileacidreceptor5(TGR5).Inthispaper,wewillreviewthecurrentknowledgeabouttheinteractionbetweenTCDCAandTGR5andtheirphysiologicalandpharmacologicalimplications.
TCDCA
TCDCAisamemberofthesolutecarrier(SLC)superfamilyoftransporters,whichareinvolvedinthetransportofvariousmoleculesacrosstheplasmamembrane.TCDCAisprimarilyexpressedintheliverandplaysacrucialroleintheenterohepaticcirculationofBAs.TCDCAisresponsiblefortheuptakeoftaurineandglycineconjugatedBAsfromtheportalveinandtheirsubsequentreabsorptionintotheliverforreprocessingandre-secretionintothebile.Inaddition,TCDCAhasbeenshowntotransportotherorganicanionssuchasbilirubinandsulfobromophthalein.TCDCAisalsoexpressedinthekidney,whereitisinvolvedinthereabsorptionofBAsfromtheurine.
TGR5
TGR5isaG-proteincoupledreceptorthatisprimarilyexpressedinthegallbladder,intestine,adiposetissue,andimmunecells.TGR5isactivatedbyBAs,particularlybylithocholicacid(LCA)anddeoxycholicacid(DCA),andalsobyanumberofothercompoundssuchastryptophanmetabolitesandsomedrugs.Uponactivation,TGR5triggersavarietyofdownstreamsignalingpathways,includingcyclicAMP(cAMP)production,extracellularsignal-regulatedkinase(ERK)activation,andcalciummobilization.TGR5activationhasbeenshowntoregulatevariousphysiologicalprocesses,suchasglucosehomeostasis,energymetabolism,andimmunefunction.
InteractionbetweenTCDCAandTGR5
TheinteractionbetweenTCDCAandTGR5hasbeenstudiedinanumberofdifferentcontexts.OneimportantaspectofthisinteractionistheroleofTCDCAinregulatingTGR5signaling.StudieshaveshownthatTCDCAcanenhanceTGR5-mediatedcAMPproductionandERKactivationinvariouscellt