P21cip-Overexpression in the Mouse β Cells Leads to the Improved Recovery from Streptozotocin-Induced Diabetes 英文参考文献.docVIP
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P21cip-Overexpression in the Mouse β Cells Leads to the Improved Recovery from Streptozotocin-Induced Diabetes 英文参考文献
P21cip-OverexpressionintheMousebCellsLeadstothe
ImprovedRecoveryfromStreptozotocin-Induced
Diabetes
JieYang1.,WeiqiZhang1.,WeiJiang1,XiaoningSun2,YuhuaHan3,MingxiaoDing1,YanShi2 ,Hongkui
Deng1,2,4
*
1The MOE Key Laboratory of Cell Proliferation and Differentiation, College of Life Sciences, Peking University, Beijing, China, 2Laboratory of Chemical Genomics,
ShenzhenGraduateSchoolofPekingUniversity,Shenzhen,China,3BeijingVitalstarBiotechCo.,Ltd.,Beijing,China,4BeijingLaboratoryAnimalResearchCenter,Beijing,
China
Abstract
Undernormalconditions,theregenerationofmousebcellsismainlydependentontheirownduplication.Althoughthere
is evidence that pancreatic progenitor cells exist around duct, whether non-b cells in the islet could also potentially
contributetobcellregenerationinvivoisstillcontroversial.Here,wedevelopedanoveltransgenicmousemodeltostudy
thepancreaticbcellregeneration,whichcouldspecificallyinhibitbcellproliferationbyoverexpressingp21cipinbcellsvia
regulationoftheTet-onsystem.Wediscoveredthatp21overexpressioncouldinhibitb-cellduplicationinthetransgenic
mice and these mice would gradually suffer from hyperglycemia. Importantly, the recovery efficiency of the p21-
overexpressingmicefromstreptozotocin-induceddiabeteswassignificantlyhigherthancontrolmice,whichisembodied
by better physiological quality and earlier emergence of insulin expressing cells. Furthermore, in the islets of these
streptozotocin-treated transgenic mice, we found a large population of proliferating cells which expressed pancreatic
duodenalhomeobox1(PDX1)butnotmarkersofterminallydifferentiatedcells.Transcriptionfactorscharacteristicofearly
pancreaticdevelopment,suchasNkx2.2andNeuroD1,andpancreaticprogenitormarkers,suchasNgn3andc-Met,could
alsobedetectedintheseislets.Thus,ourworkshowedforthefirsttimethatwhenbcellself-duplicationisrepressedbyp21
overexpression,themarkersforembryonicpancreaticprogenitorcellscouldbedetectedinislets,whichmightcontribute
totherecoveryofthesetransgenicmicefromstrept
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