[中圖分類號]R78[文獻標志碼]A[doi] 10.7518/gjkq.2025054
Theroleof the
-cateninsignalingpathwayintastebuddevelopmentandinjuryreconstruction
ZhengShuhao,LiZixia,XuXin
StateKeyLaboratoryofOralDiseasesamp;NationalCenterforStomatologyamp;NationalClinicalResearchCenterforOral Diseases,DeptofCariologyandEndodonticsWestChinaHospitaloftomatologySichuanUniversityChengdu ,China
Supportedby:NationalNatural ScienceFoundationofChina(82370947)
Correspondence:XuXin,Email:xin.xu@scu.edu.cn
[Abstract]The W n t / β -catenin signaling pathway is a major route by which mammals control embryonic development andtisue homeostasis.Thetaste buds,areceptorofthetaste system,generate taste signals tohelpthebody evaluatethe toxicityand nutritionalcomponentsoffood.Thus,tastebudsplayavitalrole inthenormalmetabolismof mammals.The W n t / β -catenin signaling pathway plays a crucial regulatory role in the development and reconstruction of tastebuds,coordinating with other signaling pathways andregulatory factors to ensure the normal development and homeostasis of taste buds and taste bud cells throughout their life cycle.This review discusses the role of the W n t / β -catenin signaling pathway in gustatory papilla development and repair.The focus is on the
-catenin signalingpathway’sregulation of progenitorand precursorcelldiferentiation,its interaction withother pathways,and maintenanceofhomeostasis.Newinsights into the molecular mechanisms of gustatory papilla development and the prevention and treatment of taste disorders are provided.
Key words]
-catenin signaling pathway; taste bud;taste cell;development; injury reconstructiol
味蕾是人類味覺感受的重要器官。味蕾通過感知味覺信號,經由神經系統將信號傳遞至中樞神經系統,從而產生味覺,主要包括酸味、甜味、苦味、咸味以及鮮味[-4]。味覺可幫助機體評估食物的毒性和營養成分,從而決定是否攝入。味覺障礙和味覺喪失等味覺異常可嚴重影響患者的生活質量,這通常與味蕾的發育和損傷修復障礙有關[57]。味蕾的發育和損傷修復不僅受到環境和遺傳因素的影響,還受到Wnt(WinglessandINT-1)、Shh(Sonichedgehog)、骨形態發生蛋白(bonemorphogeneticprotein,BMP)等信號通路的精密調控。
Wnt信號通路是機體內關鍵的保守性細胞間信號通路之一,在細胞增殖、分化和組織穩態維持與再生中發揮著重要作用[8-10]。Wnt信號通路包括經典 W n t / β -catenin信號通路和多條非經典通路,后者包括Wnt/PCP(Wnt/planar cell polarity signa-lingpathway)通路和
通路。
-catenin信號通路的主要受體為低密度脂蛋白受體(lowdensitylipoprotein receptorrelated protein,LRP)5/6和卷曲蛋白(frizzled,Fzd)[8-9]。Wnt蛋白在內質網內經過棕櫚酰化修飾后,由膜轉運蛋白Wntless介導分泌至細胞外[]。當靶細胞未接收到Wnt信號時, β -catenin與結直腸腺瘤樣息肉蛋白(adenoma-touspolyposiscoli,APC)和Axis抑制蛋白(axisinhibitionprotein,Axin)結合,并被糖原合成酶激酶(glycogen synthase kinase- ? 3 β ,GSK-3β)和酪蛋白激酶1(caseinkinase1,CK1)磷酸化。磷酸化的 β -catenin隨后被泛素-蛋白酶體系統降解,維持細胞質中游離 β -catenin的低水平狀態(圖1A)。同時,在細胞核內,轉錄抑制因子Groucho與T細胞因子(Tcellfactor,TCF)結合,抑制Wnt靶基因的表達。而當Wnt蛋白與靶細胞膜上的Fzd/LRP共受體復合體結合時,Wnt信號通路被激活,導致Axin/APC/CK1/GSK-3β降解復合體失活,細胞內 β -catenin迅速累積,進入細胞核取代Groucho并與TCF和淋巴增強因子(lymphoidenhancerfactor,LEF)結合,與其他轉錄共激活因子相互作用,從而啟動下游靶基因的轉錄[8,12](圖1B)。……