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LRRC8A在血管新生中的作用及其机制
Title:TheRoleandMechanismsofLRRC8AinAngiogenesis
Abstract:
Angiogenesis,theformationofnewbloodvesselsfrompre-existingones,playsacriticalroleinvariousphysiologicalandpathologicalprocesses.Understandingtheunderlyingmechanismsofangiogenesisiscrucialforthedevelopmentoftherapeuticinterventionsfordiseasessuchascancer,cardiovasculardisorders,anddiabeticretinopathy.Leucine-richrepeat-containingprotein8A(LRRC8A)hasemergedasakeyregulatorofcellvolumehomeostasisandhasbeenrecentlyimplicatedinangiogenesis.ThisreviewaimstoexploretheroleandmechanismsbywhichLRRC8Aregulatesangiogenesis.
Introduction:
Angiogenesisisacomplexprocessinvolvingtheproliferation,migration,anddifferentiationofendothelialcells,whicheventuallyformnewbloodvessels.Dysregulationofangiogenesisunderliesthepathogenesisofseveraldiseasessuchascancer,oculardisorders,andcardiovasculardiseases.LRRC8AisatransmembraneproteinthatformsaheteromericcomplexcalledtheVolume-RegulatedAnionChannel(VRAC).Apartfromitsroleincellvolumeregulation,recentevidencesuggeststhatLRRC8Aalsoparticipatesinangiogenesis.
RoleofLRRC8AinAngiogenesis:
LRRC8Ahasbeenshowntopromoteangiogenesisbyenhancingendothelialcellproliferation,migration,andtubeformation.KnockdownofLRRC8Ainendothelialcellsresultedindecreasedangiogenicpotential,suggestingitsimportanceinpromotingangiogenesis.Additionally,LRRC8Awasfoundtobeupregulatedintheendothelialcellsofnewlyformedbloodvesselsinvariouspathologicalconditions,furthersupportingitsroleinangiogenesis.
MechanismsofLRRC8AinAngiogenesis:
1.Regulationofcellvolume:
LRRC8AisakeycomponentoftheVRAC,whichplaysacriticalroleinmaintainingcellularvolumehomeostasis.Changesincellvolumehavebeenshowntoinfluencevariousangiogenicprocesses,includingendothelialcellmigrationandtubeformation.LRRC8A-mediatedregulationofcellvolumecould,therefore,indirectlyinfluenceangiogenesis.
2.Modulationofiontransport:
LRRC8Aformsanionchannelcomplexthatfacilitatesthetransportofchlorideionsacrossthecellmembrane.Chloridechannelshavebeendemonst