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PLoS One. 2012;7(8):e42568. doi: 10.1371/journal.pone.0042568. Epub 2012 Aug 3.

Mucosal healing and fibrosis after acute or chronic inflammation in wild type FVB-N mice and C57BL6 procollagen α1(I)-promoter-GFP reporter mice.

Author information

1
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

Erratum in

  • PLoS One. 2012;7(10). doi:10.1371/annotation/91f1d7f8-b09d-4067-943c-148e926b403b. Macnaughton, Kirk [corrected to McNaughton, Kirk K].

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.

PMID:
22880035
PMCID:
PMC3411826
DOI:
10.1371/journal.pone.0042568
[Indexed for MEDLINE]
Free PMC Article
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