教員業績データベース |
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論文種別 | 原著 |
言語種別 | 英語 |
査読の有無 | 査読あり |
表題 | Cathepsin B and D deficiency in the mouse pancreas induces impaired autophagy and chronic pancreatitis |
掲載誌名 | 正式名:Scientific reports ISSNコード:20452322 |
掲載区分 | 国外 |
巻・号・頁 | 11(1),pp.6596 |
著者・共著者 | Iwama Hideaki, Mehanna Sally, Imasaka Mai, Hashidume Shinsuke, Nishiura Hiroshi, Yamamura Kenichi, Suzuki Chigure, Uchiyama Yasuo, Hatano Etsuro, Ohmuraya Masaki |
発行年月 | 2021/03 |
概要 | The major lysosomal proteases, Cathepsin B (CTSB), Cathepsin D (CTSD) and Cathepsin L (CTSL), are implicated in autophagic activity. To investigate the role of each cathepsin in the exocrine pancreas, we generated mice in which the pancreas was specifically deficient in Ctsb, Ctsd and Ctsl. Each of these gene knockout (KO) and Ctsb;Ctsl and Ctsd;Ctsl double-knockout (DKO) mice were almost normal. However, we found cytoplasmic degeneration in the pancreatic acinar cells of Ctsb;Ctsd DKO mice, similar to autophagy related 5 (Atg5) KO mice. LC3 and p62 (autophagy markers) showed remarkable accumulation and the numbers of autophagosomes and autolysosomes were increased in the pancreatic acinar cells of Ctsb;Ctsd DKO mice. Moreover, these Ctsb;Ctsd DKO mice also developed chronic pancreatitis (CP). Thus, we conclude that both Ctsb and Ctsd deficiency caused impaired autophagy in the pancreatic acinar cells, and induced CP in mice. |