Inhibition of xCT blocks chief cell reprogramming in mouse models of acute gastric damage. (A) Diagram of drug treatments. L635 was administered to C57BL/6J mice for 3 days to induce acute gastric damage. Mice were treated with 10 mg of sulfasalazine per day, 2 days before and throughout L635 administration. Mice were killed 2 hours after the final dose of L635, and stomach tissue from untreated mice (n = 4), L635-treated mice (n = 4), and L635 + sulfasalazine–treated mice (n = 3) were harvested for histologic analysis. (B) Immunofluorescence staining for parietal cell marker H+/K+-ATPase (red), mucus granule marker GSII-lectin (green), and zymogenic granule marker GIF (blue). Scale bars: 100 μm. Magnified inset of chief cell region (right). (C) Quantification of parietal cells as determined by number of H+K+ ATPase–positive (red) cells per 20× objective field. (D) Quantification of GSII (green) and GIF (blue) dual-positive (SPEM) cells per 20× objective field (P = .004∗∗). Statistical significance was determined by 1-way analysis of variance with the Bonferroni post hoc multiple comparisons test.