title: Mucosal healing and fibrosis after acute or chronic inflammation in wild type FVB-N mice and C57BL6 procollagen α1(I)-promoter-GFP reporter mice.
abstract: BACKGROUND
  Injury and intestinal inflammation trigger wound healing responses that can restore mucosal architecture but 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 characterized mouse models.
  
  
  METHODS
  FVB-N wild type mice and C57BL6 procollagen α1(I)-GFP reporter mice were given one (DSS1) or two (DSS2) cycles of 3% DSS (5 days/cycle) followed by 7 days recovery. Histological scoring of inflammation and fibrosis were performed at DSS1, DSS1+3, DSS1+7, DSS2, DSS2+3, and DSS2+7. Procollagen α1(I)-GFP activation was assessed in DSS and also TNBS models by whole colon GFP imaging and fluorescence microscopy. Colocalization of GFP with α-smooth muscle actin (α-SMA) or vimentin was examined. GFP mRNA levels were tested for correlation with endogenous collagen α1(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 7 days of recovery. Two DSS cycles induced transmural inflammation and fibrosis in a subset of FVB-N mice but overall, did not yield more consistent, severe or sustained fibrosis. In C57BL6 mice, procollagen α1(I)-GFP reporter was activated at the end of DSS1 and through DSS+7 with more dramatic and transmural activation at DSS2 through DSS2+7, and in TNBS treated mice. In DSS and TNBS models GFP reporter expression localized to vimentin(+) cells and much fewer α-SMA(+) cells. GFP mRNA strongly correlated with collagen α1(I) mRNA.
  
  
  CONCLUSIONS
  One DSS cycle in FVB-N mice provides a model to study mucosal injury and subsequent mucosal healing. The procollagen α1(I)-GFP transgenic provides a useful model to study activation of a gene encoding a major extracellular matrix protein during acute or chronic experimental intestinal inflammation and fibrosis.
authors.affiliation: Department of Cell and Molecular Physiology, the University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America. shengli_ding@med.unc.edu
authors.forename: Shengli
authors.initials: S
authors.lastname: Ding
authors.forename: Kristen L W
authors.initials: KL
authors.lastname: Walton
authors.forename: Randall Eric
authors.initials: RE
authors.lastname: Blue
authors.forename: Kirk  K
authors.initials: K
authors.lastname: McNaughton
authors.forename: Kirk
authors.initials: K
authors.lastname: Macnaughton
authors.forename: Scott T
authors.initials: ST
authors.lastname: Magness
authors.forename: Pauline Kay
authors.initials: PK
authors.lastname: Lund
mesh_terms: D000208:Acute Disease; D000818:Animals; D000941:Antigens / Q000378:metabolism; D002908:Chronic Disease; D024042:Collagen Type I / Q000235:genetics*; D000090602:Collagen Type I, alpha 1 Chain; D003106:Colon / Q000473:pathology; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D005260:Female; D005355:Fibrosis; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000378:metabolism*; D007249:Inflammation / Q000473:pathology*; D007413:Intestinal Mucosa / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D058628:Myofibroblasts / Q000378:metabolism / Q000473:pathology; D011401:Promoter Regions, Genetic / Q000235:genetics*; D016019:Survival Analysis; D014302:Trinitrobenzenesulfonic Acid; D014746:Vimentin / Q000378:metabolism; D015431:Weight Loss; D014945:Wound Healing
chemical_list: D000941:Antigens; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D014746:Vimentin; D049452:Green Fluorescent Proteins; D014302:Trinitrobenzenesulfonic Acid; D016264:Dextran Sulfate