背景:
新型冠状病毒(-nCoV)感染性肺炎(NCIP)已对公众健康构成严重威胁。血管紧张素转换酶2((AngiotensinConvertingEnzyme2,ACE2)已被证明是介导-nCoV进入人类细胞的主要受体之一。近日有学者研究了-nCoV病毒对人体除呼吸系统之外其他脏器可能的损伤作用。
南京医院泌尿外科发表的文章表明,使用在线数据库CCLE和GTEx的数据表明肾细胞中ACE2mRNA表达水平相对较高(图一)。
免疫组化(IHC)的结果还证明尽管在肾脏中ACE2mRNA的表达水平不高,但是在肾小管细胞中,ACE2的蛋白表达水平明显很高(图二)。
同时研究者还发现ACE2在睾丸细胞中表达非常高。睾丸中ACE2的蛋白和mRNA表达几乎是体内最高的。此外,生精导管细胞和睾丸间质细胞均显示出较高的ACE2表达水平(图二)。
这些结果说明病毒可能直接结合这些ACE2阳性细胞并损害患者的肾脏和睾丸组织
美国国立卫生研究院(NIH)的研究者得到了类似结论。研究者发现ACE2主要富集在与精原细胞相对应的两个主要簇中,即睾丸间质细胞和睾丸支持细胞
(图三)。
ACE2阳性精原细胞占人类睾丸中所有精原细胞的1.28%(图四),证明人类睾丸是-nCoV感染的潜在靶点。
由于病毒对睾丸组织的潜在致病性,临床医生应注意住院期间以及以后的临床随访中患者睾丸病变的风险,尤其是对年轻患者生育力的评估和适当干预。
摘要全文
ACE2ExpressioninKidneyandTestisMayCauseKidneyandTestisDamageAfter-nCoVInfection
Abstract
InDecemberandJanuary,novelcoronavirus(-nCoV)-infectedpneumonia(NCIP)occurredinWuhan,andhasalreadyposedaseriousthreattopublichealth.ACE2(AngiotensinConvertingEnzyme2)hasbeenshowntobeoneofthemajorreceptorsthatmediatetheentryof-nCoVintohumancells,whichalsohappensinsevereacuterespiratorysyndromecoronavirus(SARS).Severalresearcheshaveindicatedthatsomepatientshaveabnormalrenalfunctionorevenkidneydamageinadditiontoinjuryinrespiratorysystem,andtherelatedmechanismisunknown.Thisarousesourinterestinwhethercoronavirusinfectionwillaffecttheurinaryandmalereproductivesystems.Hereinthisstudy,weusedtheonlinedatasetstoanalyzeACE2expressionindifferenthumanorgans.TheresultsindicatethatACE2highlyexpressesinrenaltubularcells,Leydigcellsandcellsinseminiferousductsintestis.Therefore,virusmightdirectlybindtosuchACE2positivecellsanddamagethekidneyandtesticulartissueofpatients.Ourresultsindicatethatrenalfunctionevaluationandspecialcareshouldbeperformedin-nCoVpatientsduringclinicalwork,becauseofthekidneydamagecausedbyvirusandantiviraldrugswithcertainrenaltoxicity.Inaddition,duetothepotentialpathogenicityofthevirustotesticulartissues,cliniciansshouldpayattentiontotheriskoftesticularlesionsinpatientsduringhospitalizationandlaterclinicalfollow-up,especiallytheassessmentandappropriateinterventioninyoungpatientsfertility.
scRNA-seqProfilingofHumanTestesRevealsthePresenceofACE2Receptor,aTargetforSARS-CoV-2Infection,inSpermatogonia,LeydigandSertoliCells
Abstract
InDecember,anovelcoronavirus(SARS-CoV-2)wasidentifiedinpatientswithpneumonia(calledCOVID-19)inWuhan,HubeiProvince,China.SARS-CoV-2shareshighsequencesimilarityandusesthesamecellentryreceptor,angiotensin-convertingenzyme2(ACE2),asdoessevereacuterespiratorysyndromecoronavirus(SARS-CoV).SeveralstudieshaveprovidedbioinformaticevidenceofpotentialroutesforSARS-CoV-2infectioninrespiratory,cardiovascular,digestiveandurinarysystems.However,whetherthereproductivesystemisapotentialtargetofSARS-CoV-2infectionhasnotbeendetermined.Here,weinvestigatetheexpressionpatternofACE2inadulthumantestisatthelevelofsingle-celltranscriptomes.TheresultsindicatethatACE2ispredominantlyenrichedinspermatogonia,LeydigandSertolicells.GeneontologyanalysesindicatethatGOcategoriesassociatedwithviralreproductionandtransmissionarehighlyenrichedinACE2-positivespermatogoniawhilemalegametegenerationrelatedtermsaredown-regulated.Cell-celljunctionandimmunityrelatedGOtermsareincreasedinACE2-positiveLeydigandSertolicells,butmitochondriaandreproductionrelatedGOtermsaredecreased.ThesefindingsprovideevidencethathumantestesareapotentialtargetofSARS-CoV-2infectionwhichmayhavesignificantimpactonourunderstandingofthepathophysiologyofthisrapidlyspreadingdisease.
参考文献
FanC,LiK,DingY,etal.ACE2ExpressioninKidneyandTestisMayCauseKidneyandTestisDamageAfter-nCoVInfection[J].medRxiv,:.02.12..
Wang,Z.;Xu,X.scRNA-seqProfilingofHumanTestesRevealsthePresenceofACE2Receptor,aTargetforSARS-CoV-2Infection,inSpermatogonia,LeydigandSertoliCells.Preprints,02(doi:10./preprints02..v1).
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