Inhibition of Bach1 ameliorates indomethacin-induced intestinal injury in mice.

A. Harusato, Y. Naito, T. Takagi, S. Yamada, K. Mizushima, Y. Hirai, R. Horie, K. Inoue, K. Fukumoto, I. Hirata, T. Omatsu, E. Kishimoto, K. Uchiyama, O. Handa, T. Ishikawa, S. Kokura, H. Ichikawa, A. Muto, K. Igarashi, T. Yoshikawa

研究成果: ジャーナルへの寄稿学術論文査読

23 被引用数 (Scopus)

抄録

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 Bach1 in intestinal inflammation remains unclear. In this study, the role of Bach1 in intestinal mucosal injury was elucidated using 8-week-old female C57BL/6 (wild-type) and homozygous Bach1-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 Bach1-deficient mice. Histological examination showed that the area of injured lesion was decreased in Bach1-deficient mice compared to wild-type mice. Administration of indomethacin induced expression of inflammatory chemokines such as KC, MIP1alpha and MCP1, which was suppressed in Bach1-deficient mice. Myeloperoxidase activity in the intestinal mucosa was also significantly decreased in Bach1-deficient mice. Additionally, Bach1 deficiency enhanced immunopositivity of HO-1 in the intestinal mucosa after indomethacin administration. Disruption of the Bach1 gene thus caused inhibition of mucosal injury, indicating that inhibition of Bach1 may be a novel therapeutic strategy for treating indomethacin-induced intestinal injury.

本文言語英語
ページ(範囲)149-154
ページ数6
ジャーナルJournal of Physiology and Pharmacology
60 Suppl 7
出版ステータス出版済み - 2009 12月

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