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ID 116381
タイトル別表記
ネクロプトーシスは急性膵炎の悪化を防ぐ
Necroptosis and acute pancreatitis
著者
ブンチャン, ミチトラ 徳島大学大学院医科学教育部(医学専攻)
Jaroonwitchawan, Thiranut Tokushima University
キーワード
ネクロプトーシス
急性膵炎
MLKL
RIPK3
遺伝子欠損マウス
資料タイプ
学位論文
抄録
The sensing of various extrinsic stimuli triggers the receptor-interacting protein kinase-3 (RIPK3)-mediated signaling pathway, which leads to mixed-lineage kinase-like (MLKL) phosphorylation followed by necroptosis. Although necroptosis is a form of cell death and is involved in inflammatory conditions, the roles of necroptosis in acute pancreatitis (AP) remain unclear. In the current study, we administered caerulein to Ripk3- or Mlkl-deficient mice (Ripk3-/- or Mlkl-/- mice, respectively) and assessed the roles of necroptosis in AP. We found that Ripk3-/- mice had significantly more severe pancreatic edema and inflammation associated with macrophage and neutrophil infiltration than control mice. Consistently, Mlkl-/- mice were more susceptible to caerulein-induced AP, which occurred in a time- and dose-dependent manner, than control mice. Mlkl-/- mice exhibit weight loss, edematous pancreatitis, necrotizing pancreatitis, and acinar cell dedifferentiation in response to tissue damage. Genetic deletion of Mlkl resulted in downregulation of the antiapoptotic genes Bclxl and Cflar in association with increases in the numbers of apoptotic cells, as detected by TUNEL assay. These findings suggest that RIPK3 and MLKL-mediated necroptosis exerts protective effects in AP and caution against the use of necroptosis inhibitors for AP treatment.
掲載誌名
Cell Death & Disease
ISSN
20414889
出版者
Springer Nature
12
開始ページ
601
発行日
2021-06-10
備考
内容要旨・審査要旨・論文本文の公開
本論文は,著者Michittra Boonchanの学位論文として提出され,学位審査・授与の対象となっている。
EDB ID
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
博士論文全文を含む
文科省報告番号
甲第3539号
学位記番号
甲医第1506号
学位授与年月日
2021-09-09
学位名
博士(医学)
学位授与機関
徳島大学
部局
医学系
ポストLEDフォトニクス研究所
病院