| First Author | Ding S | Year | 2012 |
| Journal | PLoS One | Volume | 7 |
| Issue | 8 | Pages | e42568 |
| PubMed ID | 22880035 | Mgi Jnum | J:189826 |
| Mgi Id | MGI:5447100 | Doi | 10.1371/journal.pone.0042568 |
| Citation | Ding S, et al. (2012) Mucosal healing and fibrosis after acute or chronic inflammation in wild type FVB-N mice and C57BL6 procollagen alpha1(I)-promoter-GFP reporter mice. PLoS One 7(8):e42568 |
| abstractText | 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 alpha1(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 alpha1(I)-GFP activation was assessed in DSS and also TNBS models by whole colon GFP imaging and fluorescence microscopy. Colocalization of GFP with alpha-smooth muscle actin (alpha-SMA) or vimentin was examined. GFP mRNA levels were tested for correlation with endogenous collagen alpha1(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 alpha1(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 alpha-SMA(+) cells. GFP mRNA strongly correlated with collagen alpha1(I) mRNA. CONCLUSIONS: One DSS cycle in FVB-N mice provides a model to study mucosal injury and subsequent mucosal healing. The procollagen alpha1(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. |
