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1、ChinJObstetGynecolPediatr(ElectronEd),August2014,Vo1.10,No.4·綜述·乙酰肝素酶與相關(guān)疾病的研究進(jìn)展羅東周容綜述王艷云審?!菊恳阴8嗡孛?HPA)是人體內(nèi)唯一能降解硫酸肝素蛋白多糖(HSPG)的一種8一葡萄糖醛酸內(nèi)切酶。HSPG是細(xì)胞外基質(zhì)(ECM)的重要組成部分,廣泛分布于細(xì)胞表面,在正常組織的發(fā)育與病理學(xué)改變的發(fā)展中具有重要作用。HPA能識(shí)別HSPG的硫酸肝素鏈(HS)并將其降解,進(jìn)而影響ECM與上皮細(xì)胞及內(nèi)皮細(xì)胞基底膜結(jié)構(gòu),釋放與HSPG結(jié)合的各種細(xì)胞因子。除通過(guò)降解HS產(chǎn)生間接生理作用外,
2、HPA還以聚集、脫落、分裂素綁定的方式影響多配體聚糖的生物效應(yīng)。另外,HPA可以增強(qiáng)信號(hào)級(jí)聯(lián)效應(yīng),促進(jìn)蛋白激酶的磷酸化和基因轉(zhuǎn)錄。因此,HPA的激活會(huì)引起一些病理生理學(xué)改變,包括炎性反應(yīng)、血管形成、腫瘤轉(zhuǎn)移、胚胎植入等。筆者擬就HPA與相關(guān)疾病的研究進(jìn)展,進(jìn)行綜述如下。【關(guān)鍵詞】乙酰肝素酶;硫酸肝素蛋白多糖;細(xì)胞外基質(zhì);相關(guān)疾病ResearchProgressofHeparanaseandRelatedDiseasesLuoDong,ZhouRong,WangYanyun.DepartmentofAPs£P(guān)soZ0g,WestChinaSecondUnive
3、rsityHospital,SichuanUniversity,Chengdu610041,SichuanProvince,China.(Correspondingauthor:WangYanyun,Email:24038062@gq.com)[Abstract]Theheparanase(HPA),ai?-D-glucuronidaseenzyme,isanuniqueenzymeofthehumanbodytOdegradeheparansulfateproteoglycan(HSPG).HSPG,animportantpartofextracellul
4、armatrix(ECM)andwidelydistributedonthecellsurface,playsanimportantroleintheprocessofgrowthanddevelopmentofnormalandpathologicaltissues.HPAcanidentifyheparansulfate(HS)chainsofHSPGanddegradethem,therebyaffectstheECMandbasementmembraneofepithelia1cellsandendothelialcells.Sovariouscyt
5、okinesbindedwithHSPGarereleased.InadditiontotheindireetphysiologicaleffectsthroughdegradingHS,HPAalsocanaffectthebiologicaleffectsofsyndecanbyaggregating,shedding,bindingmitogensligands.Furthermore,HPAcanenhancethesignal—cascadingeffect,promotetheph0sphorylationoftheproteinkinasean
6、dgenetranscription.Therefore,theactivationofHPAwillcausesomeofthepath0physiologica1changes,includinginflammation,angiogenesis,tumormetastasis,embryoimplantation.ThisarticlereviewstheprogressofHPAandrelateddiseases.[Keywords]Heparanase;Heparansulfateproteoglycan;Extraeellularmatrix;
7、Relateddiseases*ProjectNo.2O120181120046,supportedbyDoctoralFundFromMinistryofEducation;ProjectNo.2014JY0081,supportedbyApplicationFoundationofScienceandTechnologyofSichuanProvince乙酰肝素酶(heparanase,HPA)是人體內(nèi)唯一能HS產(chǎn)生間接生理作用外,HPA還以聚集、脫落、分裂降解硫酸肝素蛋白多糖(heparansulfate素綁定的方式影響多配體聚糖的生物效應(yīng)。另外,pr
8、oteoglycan,HSPG)的一種J3一D一葡萄