SUMO1、SENP1调控低氧诱导因子1α在低氧性肺动脉高压发病中的作用

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1、·polymerasechainreaction(RT-PCR)andinsituhybridizationwereusedtodeterminethemRNAexpressionofSUMO-1andSENP-1.ImmunohistochemistryandWesternblotwereadoptedtodeterminetheproteinexpressionofSUMO-1andSENP-1.Co-ImmunoprecipitationwereadoptedtodetermineSUMOylationofHIF-1αbySUMO-1.(2)Thirty-sixpa

2、tientsweredividedintothreegroups:chronicobstructivepulmonarydisease(COPD)withpulmonarypertension(PH)group(PHgroup),COPDwithoutPH(COPDgroup)andcontrolgroup.Theirlungtissueswerecollectedfromsurgicallyresectedspecimens.TheHPSRwasobservedwithmorphmetricanalysistoo.TheexpressionofHIF-1α,VEGF,S

3、UMO-1andSENP-1inpulmonaryarterioleswasexaminedbyinsituhybridizationandimmunohistochemistry.TheSUMOylationofHIF-1αbySUMO-1wasexaminedbyCo-Immunoprecipitation.Results(1)mPAPinhypoxicratsincreasedsignificantlyafter7dofhypoxia,reacheditspeakafter14dofhypoxia,andthenremainedstable.Thehypoxicra

4、tsdevelopedHPSRafter7dofhypoxia,andmoresignificantlyafter14dofhypoxia.RVHIinhypoxicratswasmarkedlyincreasedafter14dofhypoxia.HIF-1αmRNAispositivelystainedincontrolandincreaseddramaticallyafter14dofhypoxia.HIF-1αproteinwaspoorlypositiveincontrol,up-regulatedmarkedlyafter3dand7dofhypoxia,an

5、dthendeclinedslightlyafter14dand21dofhypoxia.VEGFmRNAandproteinwerepoorpositivelystainedincontrol,increasedmarkedlyafter7dofhypoxia,andthenreachedtheirpeakafter14dofexposuretohypoxia.SUMO-1mRNAandproteinexpressioninpulmonaryarteriolewallswasmarkedlyincreasedinpulmonaryarteriolewallsafter3

6、dofexposuretohypoxia,reacheditspeakafter14dofhypoxia,thenweakenedafter21dofhypoxia,butwasstillhigherthanthatinthecontrol.SENP-1mRNAandproteinwerepositivelystainedincontrol.SENP-1mRNAexpressionhadlittlechangesafterexposuretohypoxiacomparedwiththecontrol,however,SENP-1proteinexpressionwasin

7、creasedSlightlyafter3dofhypoxia,anddeclinedgraduallyafter7dofhypoxia.TheresultsofCo-immunoprecipitationshowedthatSUMOylationofHIF-1aalmostdidnothappeninlungtissuesofcontrolrats.Butitwasmarkedlypositiveafter3and7dofhypoxiainlungtissuesofrats,andreacheditspeakafter14d