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j.gastro.2022.08.048.pdf | 13.07 MB | Adobe PDF | 見る/開く |
タイトル: | Context-Dependent Roles of Hes1 in the Adult Pancreas and Pancreatic Tumor Formation |
著者: | Marui, Saiko Nishikawa, Yoshihiro https://orcid.org/0000-0002-1113-6937 (unconfirmed) Shiokawa, Masahiro Yokode, Masataka Matsumoto, Shimpei Muramoto, Yuya Ota, Sakiko Nakamura, Takeharu Yoshida, Hiroyuki Okada, Hirokazu Kuwada, Takeshi Matsumori, Tomoaki Kuriyama, Katsutoshi Fukuda, Akihisa Saur, Dieter Aoi, Takashi Uza, Norimitsu Kodama, Yuzo Chiba, Tsutomu Seno, Hiroshi |
著者名の別形: | 丸井, 彩子 西川, 義浩 塩川, 雅広 横出, 正隆 松本, 慎平 村本, 雄哉 太田, 彩貴子 中村, 武晴 吉田, 裕幸 岡田, 浩和 桒田, 威 松森, 友昭 栗山, 勝利 福田, 晃久 宇座, 徳光 妹尾, 浩 |
キーワード: | Pancreatic Ductal Adenocarcinoma PanIN Muc5ac Notch |
発行日: | Dec-2022 |
出版者: | Elsevier BV AGA Institute |
誌名: | Gastroenterology |
巻: | 163 |
号: | 6 |
開始ページ: | 1613 |
終了ページ: | 1629 |
論文番号: | e12 |
抄録: | [Background & Aims] The Notch signaling pathway is an important pathway in the adult pancreas and in pancreatic ductal adenocarcinoma (PDAC), with hairy and enhancer of split-1 (HES1) as the core molecule in this pathway. However, the roles of HES1 in the adult pancreas and PDAC formation remain controversial. [Methods] We used genetically engineered dual-recombinase mouse models for inducing Hes1 deletion under various conditions. [Results] The loss of Hes1 expression in the adult pancreas did not induce phenotypic alterations. However, regeneration was impaired after caerulein-induced acute pancreatitis. In a pancreatic intraepithelial neoplasia (PanIN) mouse model, PanINs rarely formed when Hes1 deletion preceded PanIN formation, whereas more PanINs were formed when Hes1 deletion succeeded PanIN formation. In a PDAC mouse model, PDAC formation was also enhanced by Hes1 deletion after PanIN/PDAC development; therefore, Hes1 promotes PanIN initiation but inhibits PanIN/PDAC progression. RNA sequencing and chromatin immunoprecipitation-quantitative polymerase chain reaction revealed that Hes1 deletion enhanced epithelial-to-mesenchymal transition via Muc5ac up-regulation in PDAC progression. The results indicated that HES1 is not required for maintaining the adult pancreas under normal conditions, but is important for regeneration during recovery from pancreatitis; moreover, Hes1 plays different roles, depending on the tumor condition. [Conclusions] Our findings highlight the context-dependent roles of HES1 in the adult pancreas and pancreatic cancer. |
著作権等: | © 2022 The Author(s). Published by Elsevier Inc. on behalf of the AGA Institute. This is an open access article under the CC BY license. |
URI: | http://hdl.handle.net/2433/279490 |
DOI(出版社版): | 10.1053/j.gastro.2022.08.048 |
PubMed ID: | 36075324 |
出現コレクション: | 学術雑誌掲載論文等 |
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