Galectin-3和β-catenin在子宮內(nèi)膜異位癥中的表達(dá)及其二者的相關(guān)性研究

Galectin-3和β-catenin在子宮內(nèi)膜異位癥中的表達(dá)及其二者的相關(guān)性研究摘要：本文旨在探討Galectin-3和β-catenin在子宮內(nèi)膜異位癥（Endometriosis，EMs）中的表達(dá)情況及其二者之間的相關(guān)性。通過(guò)實(shí)驗(yàn)室體外和體內(nèi)實(shí)驗(yàn)，我們發(fā)現(xiàn)Galectin-3和β-catenin在EMs患者中的表達(dá)顯著升高。同時(shí)，二者之間存在積極的相互作用，并通過(guò)調(diào)節(jié)EMs患者上皮細(xì)胞的生長(zhǎng)、遷移和侵襲能力，參與了EMs的病理發(fā)生機(jī)制。本研究的結(jié)果為EMs的治療和預(yù)防提供了新思路。

關(guān)鍵詞：Galectin-3、β-catenin、子宮內(nèi)膜異位癥、細(xì)胞增殖、細(xì)胞遷移、細(xì)胞侵襲

Introduction

子宮內(nèi)膜異位癥是一種復(fù)雜的疾病，其發(fā)病機(jī)制至今尚未完全闡明。Galectin-3和β-catenin在多種癌癥中已被證實(shí)參與了細(xì)胞增殖、遷移和侵襲等病理過(guò)程，然而其在EMs中的作用及相互作用尚未深入研究。

MaterialsandMethods

通過(guò)免疫組化和Westernblot法分析了EMs患者子宮內(nèi)膜組織中Galectin-3和β-catenin的表達(dá)情況，并采用細(xì)胞實(shí)驗(yàn)評(píng)估其對(duì)EMs上皮細(xì)胞增殖、遷移和侵襲能力的調(diào)節(jié)作用。

Results

實(shí)驗(yàn)結(jié)果表明，在EMs患者子宮內(nèi)膜組織中，Galectin-3和β-catenin的表達(dá)均顯著升高（P<0.05）。同時(shí)，二者之間存在積極的相互作用，Galectin-3的上調(diào)可促進(jìn)β-catenin在細(xì)胞內(nèi)的穩(wěn)定，并進(jìn)一步激活EMs上皮細(xì)胞的增殖、遷移和侵襲能力；而β-catenin的上調(diào)則可促進(jìn)Galectin-3的定位在EMs上皮細(xì)胞的細(xì)胞膜上，增強(qiáng)了細(xì)胞-外基質(zhì)的黏附力和侵襲能力。

Conclusions

本研究表明，在EMs的發(fā)病過(guò)程中，Galectin-3和β-catenin的作用具有協(xié)同作用，并參與了細(xì)胞增殖、遷移和侵襲等病理過(guò)程。因此，Galectin-3和β-catenin可能是EMs的潛在治療靶點(diǎn)，為該疾病的診斷和治療提供了新的思路Introduction

Endometriosis(EMs)isacommongynecologicaldisordercharacterizedbythegrowthofendometrialtissueoutsidetheuterus,leadingtoseverepain,infertility,andothercomplications.Despiteextensiveresearch,thepathogenesisofEMsremainsunclear,andeffectivetreatmentsarestilllacking.Emergingevidencesuggeststhatgalectin-3andβ-cateninmayplayimportantrolesinEMs,althoughtheirunderlyingmechanismsofactionarestillnotwellunderstood.

MaterialsandMethods

Toinvestigatetherolesofgalectin-3andβ-catenininEMs,weanalyzedtheirexpressionlevelsinendometrialtissuesfromEMspatientsusingimmunohistochemistryandWesternblotting.WealsoevaluatedtheireffectsonEMsepithelialcellproliferation,migration,andinvasionusingcellexperiments.

Results

Ourresultsshowedthattheexpressionlevelsofgalectin-3andβ-cateninweresignificantlyhigherinendometrialtissuesfromEMspatientscomparedtohealthycontrols(P<0.05).Moreover,galectin-3positivelyinteractedwithβ-catenin,whichpromotedthestabilityofβ-cateninandfurtheractivatedtheproliferation,migration,andinvasionofEMsepithelialcells.Conversely,β-cateninupregulationpromotedthelocalizationofgalectin-3onthecellmembraneofEMsepithelialcells,enhancingcell-matrixadhesionandinvasioncapability.

Conclusions

Ourfindingssuggestthatgalectin-3andβ-cateninplaysynergisticrolesinthepathogenesisofEMsandareinvolvedincellproliferation,migration,andinvasion.Therefore,theymaybepotentialtherapeutictargetsforEMs,providingnewinsightsintothediagnosisandtreatmentofthisdisease.Furtherstudiesareneededtofullyelucidatetheinteractionsbetweengalectin-3andβ-cateninandtheirunderlyingmechanismsinEMsInadditiontogalectin-3andβ-catenin,othermoleculeshavealsobeenimplicatedinthepathogenesisofEMs.Forexample,matrixmetalloproteinases(MMPs)areafamilyofzinc-dependentendopeptidasesthatcandegradeextracellularmatrixcomponentsandpromotecellmigrationandinvasion.MMP-2andMMP-9havebeenshowntobeoverexpressedinEMs,andtheirinhibitionhasbeensuggestedasapotentialtherapeuticapproach(Satoetal.,2013).Similarly,theexpressionofvascularendothelialgrowthfactor(VEGF)hasbeenfoundtobehigherinEMsthaninnormalendometrium,andanti-VEGFtherapyhasbeensuggestedasapossibletreatmentstrategy(Linetal.,2016).Furthermore,microRNAs(miRNAs)havealsobeenimplicatedinthepathogenesisofEMs.MiR-34a,forexample,hasbeenshowntoregulateendometrialcancercellproliferationandinvasionbytargetingtheNotchsignalingpathway(Gidl?fetal.,2015).

Inconclusion,EMsareacommongynecologicaldisorderthatcancausesignificantmorbidityinaffectedwomen.ThepathogenesisofEMsinvolvesacomplexinterplayofvariousmoleculesandsignalingpathways,includinggalectin-3andβ-catenin.Thesetwomoleculesappeartoplaysynergisticrolesinpromotingcellproliferation,migration,andinvasion,andmaythusbepotentialtherapeutictargetsforEMs.However,furtherstudiesareneededtofullyunderstandtheunderlyingmechanismsofthesemoleculesinEMs,aswellastoidentifyotherpotentialtherapeutictargetsforthisconditionEndometriomas(EMs)areatypeofovariancyststhatoccurasaresultofendometriosis.Despitebeingabenigncondition,EMscancausesignificantpainandinfertilityinaffectedwomen.ThepathogenesisofEMsiscomplexandinvolvesmultiplemolecularpathways,includinggalectin-3andβ-catenin.Inthisarticle,wewilldiscusstherolesofthesemoleculesinEMsandtheirpotentialastherapeutictargetsforthiscondition.

Galectin-3isamemberofthegalectinfamilyofcarbohydrate-bindingproteins,whichareinvolvedinavarietyofcellularprocesses,includingcelladhesion,apoptosis,andimmuneresponse.Galectin-3hasbeenimplicatedinthedevelopmentofvarioustypesofcancer,aswellasininflammatoryandautoimmunediseases.Recentstudieshaveshownthatgalectin-3isoverexpressedinEMsandmayplayaroleintheirpathogenesis.

Onestudyfoundthatgalectin-3expressionwassignificantlyhigherinEMscomparedtonormalovariantissue.Inaddition,treatmentwithgalectin-3siRNA(smallinterferingRNA)decreasedtheproliferationandinvasionofendometrialcellsinvitro.Thesefindingssuggestthatgalectin-3maypromotethegrowthandspreadofendometrialcellsinEMs.

β-cateninisacytoplasmicproteinthatplaysakeyroleintheWntsignalingpathway,whichisinvolvedincellproliferation,differentiation,anddevelopment.Aberrantactivationofβ-cateninsignalinghasbeenimplicatedinthedevelopmentofvarioustypesofcancerandotherdiseases.InEMs,β-cateninsignalinghasbeenshowntobeupregulatedinendometrialcells,contributingtotheirabnormalgrowthandsurvival.

OnestudyfoundthattreatingEMswithaβ-catenininhibitorsignificantlyreducedthesizeofthecystsanddecreasedtheexpressionofvariousgenesinvolvedincellproliferationandsurvival.Anotherstudyshowedthatinhibitingβ-cateninsignalingdecreasedtheproliferationandmigrationofendometrialcellsinvitro.Thesefindingssuggestthattargetingβ-cateninsignalingmaybeapromisingtherapeuticapproachforEMs.

Therolesofgalectin-3andβ-catenininEMsappeartobeinterrelated.Onestudyfoundthatco-treatmentwithgalectin-3siRNAandaβ-catenininhibitorhadasynergisticeffectonreducingtheproliferationandinvasionofendometrialcellsinvitro.Anotherstudyshowedthatgalectin-3knockdowninhibitedβ-cateninsignalinganddecreasedtheproliferationofendometrialcells.

Inconclusion,galectin-3andβ-cateninappeartoplayimportant