title: Suppression of indomethacin-induced apoptosis in the small intestine due to Bach1 deficiency.
abstract: BTB and CNC homologue 1 (Bach1) is a transcriptional repressor of heme oxygenase-1 (HO-1). This study hypothesized that Bach1 plays an important role in the indomethacin-induced apoptosis in the case of small-intestinal mucosal injury. Eight-week-old male C57BL/6 (wild-type) and homozygous Bach1-deficient C57BL/6 mice were included in this study. Mucosal injuries induced by subcutaneously administering indomethacin were evaluated macroscopically, histologically and biochemically. Indomethacin-induced injuries were improved in Bach1-deficient mice. Immunohistochemistry showed an increase in the number of HO-1-positive cells, which were mainly F4/80 positive macrophages, in Bach1-deficient mice. Indomethacin administration increased the expression of HO-1 mRNA and protein in the small intestine in Bach1-deficient mice. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) staining showed that the extent of apoptosis was suppressed in Bach1-deficent mice. In conclusion, deficiency of the Bach1 gene inhibited apoptosis and thus suppressed mucosal injury, indicating that Bach1 is a novel therapeutic target for indomethacin-induced intestinal injury.
authors.affiliation: Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.
authors.forename: Akihito
authors.initials: A
authors.lastname: Harusato
authors.forename: Yuji
authors.initials: Y
authors.lastname: Naito
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Takagi
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Uchiyama
authors.forename: Katsura
authors.initials: K
authors.lastname: Mizushima
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Hirai
authors.forename: Shinya
authors.initials: S
authors.lastname: Yamada
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Tuji
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yoriki
authors.forename: Ryusuke
authors.initials: R
authors.lastname: Horie
authors.forename: Ken
authors.initials: K
authors.lastname: Inoue
authors.forename: Kohei
authors.initials: K
authors.lastname: Fukumoto
authors.forename: Osamu
authors.initials: O
authors.lastname: Handa
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ishikawa
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kokura
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Minamiyama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ichikawa
authors.forename: Akihiko
authors.initials: A
authors.lastname: Muto
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Igarashi
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Yoshikawa
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D050976:Basic-Leucine Zipper Transcription Factors / Q000172:deficiency* / Q000235:genetics; D053148:Caspase 3 / Q000378:metabolism; D004789:Enzyme Activation; D057075:Enzyme Assays; D017353:Gene Deletion; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D007082:Ileum / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007213:Indomethacin / Q000009:adverse effects*; D008297:Male; D008665:Metalloporphyrins / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D011524:Protoporphyrins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D014456:Ulcer / Q000139:chemically induced / Q000473:pathology*
chemical_list: C486316:Bach1 protein, mouse; D050976:Basic-Leucine Zipper Transcription Factors; D008665:Metalloporphyrins; D011524:Protoporphyrins; D014409:Tumor Necrosis Factor-alpha; C032628:tin protoporphyrin IX; D051547:Heme Oxygenase-1; D053148:Caspase 3; D007213:Indomethacin