Pharmacologic activation of the PXR attenuates the development of fibrosis after colonic injury. (A) WT mice were administered DSS for 5 days to induce colonic injury and then switched to regular drinking water and injected interperitoneally with the mouse-specific PXR agonist pregnenolone-15-alpha carbonitrile (PCN) every other day for 25 days. (B) Weight recovery and (C) gross colonic length and thickness in WT(Nr1i2+/+) and Nr1i2-/- mice 25 days after withdrawal of DSS. (D) Representative images of Masson’s trichrome staining and (E) quantification of fibrosis in the colon after injury and subsequent treatment with PCN or vehicle (n = 5–6 per group; scale bar = 100 μm). The expression of (F) the PXR target gene Cyp3a11, (G) fibrotic genes Acta2, Col1a1, Col1a2, and Col3a1, and (H) innate immune genes Csf2, Csf3, Cxcl1, and Cxcl2 in the healing colon of mice (10 days withdrawal of DSS; n = 5–6 per group). Data are represented as mean ± standard error of the mean. Student t test (C, E, and F) and one-way analysis of variance with Tukey post hoc test (H). ∗P < .05, ∗∗P < .01, ∗∗∗P < .001.