Exocrine tissue-driven TFF2 prevents apoptotic cell death of endocrine lineage during pancreas organogenesis

• 平田, 耕司

  Department of Hepato-Biliary-Pancreatic Surgery and Transplantation, Kyoto University Graduate School of Medicine･Department of Clinical Application, Center for iPS cell Research and Application, Kyoto

• 児玉, 創太

  Department of Hepato-Biliary-Pancreatic Surgery and Transplantation, Kyoto University Graduate School of Medicine･Department of Clinical Application, Center for iPS cell Research and Application, Kyoto

• 増井, 俊彦

  Department of Clinical Application, Center for iPS cell Research and Application, Kyoto

• 山本, 拓也

  Department of Clinical Application, Center for iPS cell Research and Application, Kyoto

• 上本, 伸二

  Department of Hepato-Biliary-Pancreatic Surgery and Transplantation, Kyoto University Graduate School of Medicine･Department of Clinical Application, Center for iPS cell Research and Application, Kyoto

• 川口, 義弥

  Department of Hepato-Biliary-Pancreatic Surgery and Transplantation, Kyoto University Graduate School of Medicine･Department of Clinical Application, Center for iPS cell Research and Application, Kyoto

• Goto, Toshihiko

  Department of Hepato-Biliary-Pancreatic Surgery and Transplantation, Kyoto University Graduate School of Medicine･Department of Clinical Application, Center for iPS cell Research and Application, Kyoto

• Yoshida, Masahiro

  Department of Hepato-Biliary-Pancreatic Surgery and Transplantation, Kyoto University Graduate School of Medicine･Department of Clinical Application, Center for iPS cell Research and Application, Kyoto

• Masui, Toshihiko

  Department of Hepato-Biliary-Pancreatic Surgery and Transplantation, Kyoto University Graduate School of Medicine

• Yamamoto, Takuya

  Department of Life Science Frontiers, Center for iPS Cell Research and Application, Kyoto

• Uemoto, Shinji

  Department of Hepato-Biliary-Pancreatic Surgery and Transplantation, Kyoto University Graduate School of Medicine

• Kawaguchi, Yoshiya

  Department of Clinical Application, Center for iPS cell Research and Application, Kyoto

抄録

During embryogenesis, exocrine and endocrine pancreatic tissues are formed in distinct regions within the branched ductal structure in mice. We previously reported that exocrine-specific inactivation of Pdx1 by Elastase-Cre caused not only hypoplastic exocrine formation but also substantial endocrine defects resulting in diabetic phenotype, indicating the existence of an exocrine-driven factor(s) that regulates proper endocrine development. In this study, we identified Trefoil Factor 2 (TFF2) as an exocrine gene expressed from embryonic day 16.5 to adulthood in normal mice but significantly less in our Pdx1 mutants. Using in vitro explant culture of embryonic pancreatic tissue, we demonstrated that TFF2 prevented the apoptosis of insulin-producing cells but that antagonizing CXCR4, a known TFF2 receptor, suppressed this anti-apoptotic effect in the mutants. Furthermore, the antagonist in normal pancreatic tissue accelerated the apoptosis of insulin-producing cells, indicating that the TFF2/CXCR4 axis maintains embryonic insulin-producing cells in normal development. TFF2 also suppressed the apoptosis of Nkx6.1+ endocrine precursors in mutant pancreata, but this effect was unperturbed by the CXCR4 antagonist, suggesting the existence of an unknown receptor for TFF2. These findings suggest TFF2 is a novel exocrine factor that supports the survival of endocrine cells in the multiple stages of organogenesis through distinct receptors.

収録刊行物

• Scientific Reports

  Scientific Reports 9 2019-02-07

  Nature Publishing Group

キーワード

• Multidisciplinary

詳細情報

• CRID: 1050845763139431552
• NII論文ID: 120006557515
• ISSN: 20452322
• DOI: 10.1038/s41598-018-38062-9
• HANDLE: 2433/236480
• Web Site: https://www.nature.com/articles/s41598-018-38062-9.pdf
• Web Site: https://www.nature.com/articles/s41598-018-38062-9
• 本文言語コード: en
• 資料種別: journal article
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