Mucosal Healing and Fibrosis after Acute or Chronic Inflammation in Wild Type FVB-N Mice and C57BL6 Procollagen α1(I)-Promoter-GFP Reporter Mice 英文参考文献.docVIP

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Mucosal Healing and Fibrosis after Acute or Chronic Inflammation in Wild Type FVB-N Mice and C57BL6 Procollagen α1(I)-Promoter-GFP Reporter Mice 英文参考文献.doc

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Mucosal Healing and Fibrosis after Acute or Chronic Inflammation in Wild Type FVB-N Mice and C57BL6 Procollagen α1(I)-Promoter-GFP Reporter Mice 英文参考文献

MucosalHealingandFibrosisafterAcuteorChronic InflammationinWildTypeFVB-NMiceandC57BL6 Procollagena1(I)-Promoter-GFPReporterMice ShengliDing1*,KristenL.W.Walton2,RandallEricBlue1,KirkMacNaughton3,ScottT.Magness4 ,Pauline KayLund1 1DepartmentofCellandMolecularPhysiology,theUniversityofNorthCarolinaatChapelHill,ChapelHill,NorthCarolina,UnitedStatesofAmerica, 2Departmentof Biology,MissouriWesternStateUniversity, St.Joseph,Missouri,UnitedStates ofAmerica, 3HistologyCoreFacility,Department ofCellandMolecularPhysiology,the UniversityofNorthCarolinaatChapelHill,ChapelHill,NorthCarolina,UnitedStatesofAmerica,4DivisionofGastroenterologyandHepatology,DepartmentofMedicine, UniversityofNorthCarolinaatChapelHill,ChapelHill,NorthCarolina,UnitedStatesofAmerica Abstract Background:Injuryandintestinalinflammationtriggerwoundhealingresponsesthatcanrestoremucosalarchitecturebut if chronic, can promote intestinal fibrosis. Intestinal fibrosis is a major complication of Crohn’s disease. The cellular and molecular basis of mucosal healing and intestinal fibrosis are not well defined and better understanding requires well characterizedmousemodels. Methods: FVB-N wild type mice and C57BL6 procollagen a1(I)-GFP reporter mice were given one (DSS1) or two (DSS2) cycles of 3% DSS (5days/cycle) followed by 7days recovery. Histological scoring of inflammation and fibrosis were performedatDSS1,DSS1+3,DSS1+7,DSS2,DSS2+3,andDSS2+7.Procollagena1(I)-GFPactivationwasassessedinDSSand alsoTNBSmodelsbywholecolonGFPimagingandfluorescencemicroscopy.ColocalizationofGFPwitha-smoothmuscle actin (a-SMA) or vimentin was examined. GFP mRNA levels were tested for correlation with endogenous collagen a1(I) mRNA. Results: Males were more susceptible to DSS-induced disease and mortality than females. In FVB-N mice one DSS cycle induced transient mucosal inflammation and fibrosis that resolved by 7days of recovery. Two DSS cycles induced transmural inflammation and fibrosis in a subset of FVB-N mic