Deletion of Nr1i2 in the mesenchymal compartment, but not epithelial compartment, enhances fibrotic responses in the colon after injury. (A) Experimental outline of Vil1-Cre:Nr1i2fl/fl (Nr1i2ΔVil1) and Nr1i2fl/fl (Cre-) control mice administered DSS for 5 days and then allowed to heal for 25 days (∗indicates the different analysis time points). (B) Western blot analysis of PXR protein in freshly isolated colonic intestinal epithelial cells. (C) Weight recovery and (D) gross colonic length and thickness in Nr1i2ΔVil1and Nr1i2fl/f mice 25 days after withdrawal of DSS. (E) Representative images of Masson’s trichrome staining and quantification of fibrosis in the colon after injury in Nr1i2ΔVil1and Nr1i2fl/fl control mice (n = 4 per group). The expression of (F) fibrotic genes Acta2, Col1a1, Col1a2, and Col3a1 and (G) colonic lamina propria neutrophil infiltration and (H) innate immune gene expression in the healing colonic lamina propria of Nr1i2ΔVil1 and Nr1i2fl/fl mice 10 days after withdrawal of DSS (n = 4 per group). (I) Experimental outline of tamoxifen administration to Col1a2-CreERT:Nr1i2fl/fl (Nr1i2ΔCol1) and Nr1i2fl/fl (Cre-) control mice that were then given DSS for 5 days and then allowed to heal for 25 days while receiving tamoxifen throughout experiment as indicated. (J) Western blot analysis of PXR protein in freshly isolated colonic fibroblasts. (K) Weight recovery and (L) gross colonic length and thickness in Nr1i2ΔCol1a2 and Nr1i2fl/f mice 25 days after withdrawal of DSS. (M) Representative images of Masson’s trichrome staining and quantification of fibrosis in the colon after injury in Nr1i2ΔCol1a2 and Nr1i2fl/fl control mice (n = 6 per group). The expression of (N) fibrotic genes Acta2, Col1a1, Col1a2, and Col3a1 and (O) colonic lamina propria neutrophil infiltration and (P) innate immune gene expression in the healing colonic lamina propria of Nr1i2ΔCol1a2 and Nr1i2fl/fl mice 10 days after withdrawal of DSS (n = 4 per group). Data are presented as mean ± standard error of the mean. Student t test (C–G, K–O). ∗P < .05,∗∗P < .01,∗∗∗P < .001.