Inhibition of Bach1 ameliorates indomethacin-induced intestinal injury in mice

BTB and CNC homolog 1 (Bach1) is a transcriptional repressor of heme oxygenase-1 (HO-1). It plays an important role in the feedback regulation of HO-1 expression, which protects cells from various insults including oxidative stress and inflammatory cytokines. However, the role of Bachl in intestinal inflammation remains unclear. In this study, the role of Bachl in intestinal mucosal injury was elucidated using 8-week-old female C57BL/6 (wild-type) and homozygous Bachl-deficient C57BL/6 mice. Intestinal mucosal injuries induced by a single subcutaneous administration of indomethacin were evaluated macroscopically, histologically, and biochemically. Mucosal protein content and chemokine mRNA levels were determined by real-time PCR. Our results showed that the indomethacin-induced intestinal injury was remarkably improved in Bachl-deficient mice. Histological examination showed that the area of injured lesion was decreased in Bachl-deficient mice compared to wild-type mice. Administration of indomethacin induced expression of inflammatory chemokines such as KC, MIPIα and MCP1, which was suppressed in Bachl-deficient mice. Myeloperoxidase activity in the intestinal mucosa was also significantly decreased in Bachl-deficient mice. Additionally, Bachl deficiency enhanced immunopositivity of HO-1 in the intestinal mucosa after indomethacin administration. Disruption of the Bachl gene thus caused inhibition of mucosal injury, indicating that inhibition of Bachl may be a novel therapeutic strategy for treating indomethacin-induced intestinal injury.