Protective Role of R-spondin1, an Intestinal Stem Cell Growth Factor, against Radiation-Induced Gastrointestinal Syndrome in Mice 英文参考文献.docVIP

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Protective Role of R-spondin1, an Intestinal Stem Cell Growth Factor, against Radiation-Induced Gastrointestinal Syndrome in Mice 英文参考文献.doc

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Protective Role of R-spondin1, an Intestinal Stem Cell Growth Factor, against Radiation-Induced Gastrointestinal Syndrome in Mice 英文参考文献

ProtectiveRoleofR-spondin1,anIntestinalStemCell GrowthFactor,againstRadiation-Induced GastrointestinalSyndromeinMice PayelBhanja1,SubhrajitSaha1,RafiKabarriti1,LaibinLiu1,NamitaRoy-Chowdhury2,3,JayantaRoy- Chowdhury2,3,RaniS.Sellers4,AlanA.Alfieri1,ChandanGuha1,4* 1DepartmentofRadiationOncology,AlbertEinsteinCollegeofMedicine,Bronx,NewYork,UnitedStatesofAmerica,2DepartmentofMedicine,AlbertEinsteinCollegeof Medicine, Bronx, New York, United States of America, 3Department of Genetics, Albert Einstein College of Medicine, Bronx, New York, United States of America, 4DepartmentofPathologyandMontefioreMedicalCenter,AlbertEinsteinCollegeofMedicine,Bronx,NewYork,UnitedStatesofAmerica Abstract Background:Radiation-inducedgastrointestinalsyndrome(RIGS)resultsfromacombinationofdirectcytocidaleffectson intestinalcryptandendothelialcellsandsubsequentlossofthemucosalbarrier,resultinginelectrolyteimbalance,diarrhea, weight loss, infection and mortality. Because R-spondin1 (Rspo1) acts as a mitogenic factor for intestinal stem cells, we hypothesizedthatsystemicadministrationofRspo1wouldamplifytheintestinalcryptcellsandacceleratetheregeneration oftheirradiatedintestine,thereby,amelioratingRIGS. MethodsandFindings:MaleC57Bl/6micereceivedrecombinantadenovirusexpressinghumanR-spondin1(AdRspo1)or E.coliLacz(AdLacz),1–3daysbeforewholebodyirradiation(WBI)orabdominalirradiation(AIR).Post-irradiationsurvival wasassessed by KaplanMeieranalysis. RIGS was assessed by histological examinationofintestine afterhematoxilin and eosin staining, immunohistochemical staining of BrdU incorporation, Lgr5 and b-catenin expression and TUNEL staining. The xylose absorption test (XAT) was performed to evaluate the functional integrity of the intestinal mucosal barrier. In ordertoexaminetheeffectofR-spondin1ontumorgrowth,AdRspo1andAdLacZwasadministeredintheanimalshaving palpable tumor and then exposed to AIR. There was a significant increase in survival in AdRspo1 cohorts compared to AdLacZ (p,0.003) cont