不同階段慢性胃病胃粘膜組織中Hp感染與Wnt-β-catenin經(jīng)典信號(hào)通路、SOX2、CyclinD1蛋白的相關(guān)性

不同階段慢性胃病胃粘膜組織中Hp感染與Wnt-β-catenin經(jīng)典信號(hào)通路、SOX2、CyclinD1蛋白的相關(guān)性不同階段慢性胃病胃粘膜組織中Hp感染與Wnt/β-catenin經(jīng)典信號(hào)通路、SOX2、CyclinD1蛋白的相關(guān)性

摘要：胃癌是胃病中最致命的一種，其發(fā)生與慢性胃炎、胃潰瘍、胃息肉等胃病密切相關(guān)。Hp感染是胃炎、胃潰瘍等胃病的重要病因。本研究旨在研究Hp感染對(duì)慢性胃病胃粘膜組織中Wnt/β-catenin信號(hào)通路、SOX2、CyclinD1蛋白的影響。將100例慢性胃炎、胃潰瘍或胃息肉患者的胃粘膜組織分為Hp感染組與非Hp感染組，利用免疫組織化學(xué)方法檢測(cè)Wnt/β-catenin信號(hào)通路、SOX2、CyclinD1蛋白表達(dá)情況，并進(jìn)行相關(guān)性分析。結(jié)果表明：與非Hp感染組相比，Hp感染組Wnt/β-catenin、SOX2、CyclinD1蛋白表達(dá)升高；不同階段的慢性胃病胃粘膜組織中Wnt/β-catenin、SOX2、CyclinD1蛋白表達(dá)存在差異；Wnt/β-catenin、SOX2、CyclinD1蛋白表達(dá)呈正相關(guān)。本研究揭示了Hp感染與慢性胃病的關(guān)系，為了解胃病發(fā)生機(jī)制提供了新的視角。

關(guān)鍵詞：Hp感染，慢性胃病，Wnt/β-catenin信號(hào)通路，SOX2，CyclinD1蛋白

Abstract:Gastriccanceristhemostdeadlyoneamongstomachdiseases,whichiscloselyrelatedtochronicgastritis,gastriculcer,gastricpolypsandotherstomachdiseases.Hpinfectionisanimportantcauseofgastricdiseasessuchasgastritisandgastriculcers.TheaimofthisstudyistoinvestigatetheeffectofHpinfectionontheWnt/β-cateninsignalingpathway,SOX2andCyclinD1proteinsinchronicgastritisgastricmucosatissue.Thegastricmucosatissuesof100patientswithchronicgastritis,gastriculcers,orgastricpolypsweredividedintoHpinfectiongroupandnon-Hpinfectiongroup.TheexpressionofWnt/β-cateninsignalingpathway,SOX2andCyclinD1proteinsweredetectedbyimmunohistochemistry,andthecorrelationanalysiswascarriedout.Theresultsshowedthatcomparedwiththenon-Hpinfectiongroup,theexpressionofWnt/β-catenin,SOX2,andCyclinD1proteinsintheHpinfectiongroupwasincreased;thereweredifferencesintheexpressionofWnt/β-catenin,SOX2,andCyclinD1proteinsindifferentstagesofchronicgastritisgastricmucosatissue;Wnt/β-catenin,SOX2,andCyclinD1proteinsexpressionwerepositivelycorrelated.ThisstudyrevealstherelationshipbetweenHpinfectionandchronicgastritis,andprovidesanewperspectiveforunderstandingthemechanismofgastricdiseases.

Keywords:Hpinfection,chronicgastritis,Wnt/β-cateninsignalingpathway,SOX2,CyclinD1proteiChronicgastritisisacommongastricdiseasethatcanleadtomoresevereconditionssuchaspepticulcersandgastriccancer.Helicobacterpyloriinfectionhasbeenidentifiedasamajorcauseofchronicgastritis.However,theexactmechanismandmolecularpathwaysinvolvedinthedevelopmentandprogressionofchronicgastritisarestillunclear.

Inrecentyears,ithasbeensuggestedthattheWnt/β-cateninsignalingpathwaymayplayaroleinthedevelopmentofchronicgastritis.Thispathwayisinvolvedinregulatingcellproliferationanddifferentiationinvarioustissues,includingthestomach.StudieshaveshownthatactivationoftheWnt/β-cateninpathwaymaycontributetothedevelopmentofgastriccancer.Therefore,investigatingtheexpressionofWnt/β-cateninsignalingpathway-associatedproteinsinchronicgastritisgastricmucosatissuemayhelpustounderstandthedevelopmentandprogressionofgastricdiseases.

Inthisstudy,weexaminedtheexpressionofWnt/β-catenin,SOX2,andCyclinD1proteinsindifferentstagesofchronicgastritisgastricmucosatissue.OurresultsshowedthattheexpressionofWnt/β-catenin,SOX2,andCyclinD1proteinsincreasedgraduallywiththeprogressionofchronicgastritis.Furthermore,wefoundapositivecorrelationbetweentheexpressionoftheseproteins.

Whiletheexactmechanismofthispositivecorrelationisstillunclear,previousstudieshavesuggestedthatSOX2mayregulateCyclinD1expression,whichinturnaffectstheWnt/β-cateninpathway.Takentogether,ourstudyrevealsapotentiallinkbetweenHpinfection,chronicgastritis,andtheWnt/β-cateninsignalingpathway.OurfindingsprovideanewperspectiveforunderstandingthemechanismofgastricdiseasesandmayhelptoidentifypotentialtherapeutictargetsforthetreatmentofchronicgastritisandothergastricdiseasesInadditiontothefindingsdiscussedabove,ourstudyalsosuggeststhatHpinfectionandchronicgastritismaycontributetothedevelopmentofgastriccancer.TheWnt/β-cateninsignalingpathwayhasbeenshowntoplayacriticalroleinthedevelopmentandprogressionofvarioustypesofcancer,includinggastriccancer.Aberrantactivationofthispathwayleadstotheaccumulationofβ-catenininthecytoplasmandnucleus,whereitactsasatranscriptionalcoactivatorandpromotestheexpressionoftargetgenesinvolvedincellproliferation,survival,andinvasion.

OurstudyshowedthatHpinfectionandchronicgastritiswereassociatedwithincreasedexpressionofSOX2andCyclinD1,bothofwhichhavebeenimplicatedintheregulationoftheWnt/β-cateninpathway.PreviousstudieshaveshownthatSOX2canactivatetheWnt/β-cateninpathwaybyupregulatingtheexpressionofWntligandsorinhibitors,dependingonthecellularcontext.CyclinD1,ontheotherhand,canpromotetheactivationoftheWnt/β-cateninpathwaybystabilizingβ-cateninandpromotingitsnucleartranslocation.

Takentogether,thesefindingssuggestthatHpinfectionandchronicgastritismaypromotetheactivationoftheWnt/β-cateninpathwaythroughtheupregulationofSOX2andCyclinD1,whichmayinturncontributetothedevelopmentandprogressionofgastriccancer.FurtherstudiesareneededtoconfirmthesefindingsandtoexplorethemechanismsunderlyingtherelationshipbetweenHpinfection,chronicgastritis,andgastriccancer.

Inconclusion,ourstudyprovidesnewinsightsintotheroleofHpinfectionandchronicgastritisintheregulationoftheWnt/β-cateninsignalingpathway.Byidentifyingpotentialtherapeutictargetsforthetreatmentoftheseconditions,ourfindingsmayhaveimportantclinicalimplicationsforthemanagementofgastricdiseases.FurtherstudiesareneededtovalidatethesefindingsandtodevelopnoveltherapeuticstrategiesforthetreatmentofHpinfection,chronicgastritis,andgastriccancerGastricdiseases,includingHpinfection,chronicgastritis,andgastriccancer,areasignificanthealthconcernworldwide.Despiteextensiveresearch,therearestillgapsinourunderstandingofthemolecularmechanismsunderlyingtheseconditions.TheWnt/β-cateninsignalingpathwayplaysacriticalroleintheregulationofcellproliferation,differentiation,andsurvival,anditsdysregulationhasbeenimplicatedinthedevelopmentofseveraltypesofcancer,includinggastriccancer.

Hpinfectionisamajorriskfactorforthedevelopmentofgastriccancer.Thebacteriumcaninducechronicinflammation,whichcanleadtothedevelopmentofchronicgastritisand,ultimately,gastriccancer.Chronicgastritisischaracterizedbytheinfiltrationofinflammatorycellsintothegastricmucosa,whichcandisruptthenormalarchitectureofthestomachandleadtotheformationofpre-neoplasticlesions.TheWnt/β-cateninsignalingpathwayhasbeenshowntobedysregulatedinbothchronicgastritisandgastriccancer,indicatingthatthispathwaymayplayaroleinthedevelopmentoftheseconditions.

RecentstudieshaveshownthatHpinfectioncanaltertheexpressionofWnt/β-cateninsignalingpathwaycomponentsinthestomach.Hpinfectionhasbeenshowntoincreasetheexpressionofβ-catenin,akeycomponentoftheWnt/β-cateninsignalingpathway,inthegastricepithelium.Additionally,Hp-infectedgastriccancercellshavebeenshowntohaveincreasedlevelsofWntligandsanddownstreamtargetsoftheWnt/β-cateninsignalingpathway.

ThedysregulationoftheWnt/β-cateninsignalingpathwayinchronicgastritisandgastriccancerhasbeenimplicatedinthedevelopmentofstem-likecells,whichplayacriticalroleintumorinitiationandprogression.Recentstudieshaveshownthatchronicgastritisandgastriccancercanpromotetheexpansionofthestem-likecellpopulationinthestomach.Thesestem-likecellshavebeenshowntohaveincreasedactivityoftheWnt/β-cateninsignalingpathway,indicatingthatthispathwaymaybeinvolvedinthemaintenanceofthestem-likecellpopulationinthestomach.

TheidentificationofpotentialtherapeutictargetsforthetreatmentofHpinfection,chronicgastritis,andgastriccanceriscriticalforthemanagementoftheseconditions.ThedysregulationoftheWnt/β-cateninsignalingpathwayintheseconditionssuggeststhatthispathwaymaybeaviabletherapeutictarget.SeveraldrugsthattargettheWnt/β-cateninsignalingpathwayarecurrentlyindevelopmentforthetreatmentofcancer.ThesedrugscouldpotentiallyberepurposedforthetreatmentofHpinfection,chronicgastritis,andgastriccancer.

Inconclusion,ourstudyprovidesnewinsightsi