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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
Author
Boonchan, Michittra Tokushima University
Jaroonwitchawan, Thiranut Tokushima University
Keywords
ネクロプトーシス
急性膵炎
MLKL
RIPK3
遺伝子欠損マウス
Content Type
Thesis or Dissertation
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.
Journal Title
Cell Death & Disease
ISSN
20414889
Publisher
Springer Nature
Volume
12
Start Page
601
Published Date
2021-06-10
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
TextVersion
ETD
MEXT report number
甲第3539号
Diploma Number
甲医第1506号
Granted Date
2021-09-09
Degree Name
Doctor of Medical Science
Grantor
Tokushima University
departments
Medical Sciences
Institute of Post-LED Photonics
University Hospital