ID | 116381 |
Title Alternative | ネクロプトーシスは急性膵炎の悪化を防ぐ
Necroptosis and acute pancreatitis
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Author |
Boonchan, Michittra
Tokushima University
Arimochi, Hideki
Tokushima University
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Kobayashi, Tomoko
Tokushima University
Uehara, Hisanori
Tokushima University
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Jaroonwitchawan, Thiranut
Tokushima University
Tsukumo, Shin-ichi
Tokushima University
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Yasutomo, Koji
Tokushima University
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Keywords | ネクロプトーシス
急性膵炎
MLKL
RIPK3
遺伝子欠損マウス
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Content Type |
Thesis or Dissertation
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Description | 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.
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Journal Title |
Cell Death & Disease
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ISSN | 20414889
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Publisher | Springer Nature
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Volume | 12
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Start Page | 601
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Published Date | 2021-06-10
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Remark | 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 | |
DOI (Published Version) | |
URL ( Publisher's Version ) | |
FullText File | |
language |
eng
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TextVersion |
ETD
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MEXT report number | 甲第3539号
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Diploma Number | 甲医第1506号
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Granted Date | 2021-09-09
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Degree Name |
Doctor of Medical Science
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Grantor |
Tokushima University
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departments |
Medical Sciences
Institute of Post-LED Photonics
University Hospital
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