caa a22 4500 445888326 CHVBK 20180317145607.0 cr unu---uuuuu 170323e20110301xx s 000 0 eng 10.1007/s00535-010-0355-9 doi (NATIONALLICENCE)springer-10.1007/s00535-010-0355-9 CITED2 is activated in ulcerative colitis and induces p53-dependent apoptosis in response to butyric acid [Elektronische Daten] [Tsutomu Yoshida, Tsukasa Sekine, Ken-ichi Aisaki, Tetuo Mikami, Jun Kanno, Isao Okayasu] Background: In ulcerative colitis (UC), Fusobacterium varium is significantly detected in patients' mucosa, and butyric acid (BA), abundantly produced by the bacterium, activates the p53 system and induces epithelial apoptosis, as we previously reported. However, factors active in the link between BA and p53 have yet to be clarified. Here, we identified a gene activated by BA specifically in UC-associated cancer cell lines and ascertained the mechanism of its activation of p53. Methods: cDNA microarray analysis based on the Percellome (per cell normalization) method was performed on BA-stimulated UC-associated cancers and sporadic colorectal cancer cell lines under conditions mimicking colonic epithelium UC. For validation of microarray results, molecular, biochemical, and histopathological analyses were performed. Results: We found the CBP/p300-interacting transactivator with glutamic acid/asparagine-rich carboxy-terminal domain 2 (CITED2) to be specifically upregulated in UC-associated cancer cell lines by BA treatment, at both mRNA and protein expression levels. CITED2 could be shown to induce p53 acetylation and p53-dependent apoptosis, accompanied by binding of CBP/p300. BA-dependent apoptosis was suppressed by an inhibitor of monocarboxylate transporter-1 and an siRNA for p53. In inflammatory foci of UC, histologically evident inflammatory activity and CITED2 expression were significantly correlated. Conclusions: CITED2 was identified as UC-associated protein by cDNA microarray based on the Percellome method under UC-mimicking conditions in vitro. CITED2 activation may induce mucosal apoptosis and erosion by activating p53 and thus play a critical role in linking enteric bacteria with mucosal inflammation in UC. Springer, 2010 Ulcerative colitis nationallicence Inflammation nationallicence Apoptosis nationallicence CITED2 nationallicence Butyric acid nationallicence p53 nationallicence CBP/p300 nationallicence BA : Butyric acid nationallicence CITED2 : CBP/p300-interacting transactivator with glutamic acid/asparagine-rich carboxy-terminal domain 2 nationallicence 4CHC : 4-Hydroxycinnamate nationallicence IL-10 : Interleukin-10 nationallicence MCT1 : Monocarboxylate transporter-1 nationallicence q-RT-PCR : Quantitative reverse transcription PCR nationallicence sCRC : Sporadic colorectal cancer nationallicence UC : Ulcerative colitis nationallicence UCCA : Ulcerative colitis-associated cancer nationallicence Yoshida Tsutomu Department of Pathology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, 252-0374, Sagamihara, Kanagawa, Japan aut Sekine Tsukasa Department of Pathology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, 252-0374, Sagamihara, Kanagawa, Japan aut Aisaki Ken-ichi Division of Cellular and Molecular Toxicology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, 158-5801, Tokyo, Japan aut Mikami Tetuo Department of Pathology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, 252-0374, Sagamihara, Kanagawa, Japan aut Kanno Jun Division of Cellular and Molecular Toxicology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, 158-5801, Tokyo, Japan aut Okayasu Isao Department of Pathology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, 252-0374, Sagamihara, Kanagawa, Japan aut Journal of Gastroenterology Springer Japan 46/3(2011-03-01), 339-349 0944-1174 46:3<339 2011 46 535 https://doi.org/10.1007/s00535-010-0355-9 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00535-010-0355-9 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Yoshida Tsutomu Department of Pathology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, 252-0374, Sagamihara, Kanagawa, Japan aut NATIONALLICENCE 700 1- Sekine Tsukasa Department of Pathology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, 252-0374, Sagamihara, Kanagawa, Japan aut NATIONALLICENCE 700 1- Aisaki Ken-ichi Division of Cellular and Molecular Toxicology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, 158-5801, Tokyo, Japan aut NATIONALLICENCE 700 1- Mikami Tetuo Department of Pathology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, 252-0374, Sagamihara, Kanagawa, Japan aut NATIONALLICENCE 700 1- Kanno Jun Division of Cellular and Molecular Toxicology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, 158-5801, Tokyo, Japan aut NATIONALLICENCE 700 1- Okayasu Isao Department of Pathology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, 252-0374, Sagamihara, Kanagawa, Japan aut NATIONALLICENCE 773 0- Journal of Gastroenterology Springer Japan 46/3(2011-03-01), 339-349 0944-1174 46:3<339 2011 46 535 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer