Necroptosis protects against exacerbation of acute pancreatitis.

Cell Death & Disease
Michittra BoonchanKoji Yasutomo

Abstract

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 necrop...Continue Reading

References

Mar 13, 2003·World Journal of Gastroenterology : WJG·Shi-Ping DingChang Jin
Mar 1, 2012·Molecular Medicine·Andreas LinkermannStefan Krautwald
Mar 17, 2012·Proceedings of the National Academy of Sciences of the United States of America·Jie ZhaoZheng-Gang Liu
Mar 31, 2012·American Journal of Physiology. Gastrointestinal and Liver Physiology·Lili GuoJohn A Williams
Apr 30, 2013·Gastroenterology·Markus M Lerch, Fred S Gorelick
Jul 10, 2013·Cell Research·Jianfeng WuJiahuai Han
Jul 31, 2013·Current Opinion in Gastroenterology·Raghuwansh P SahAshok K Saluja
Oct 2, 2013·Annual Review of Physiology·Dana E ChristoffersonJunying Yuan
Jan 17, 2015·Nature·Manolis Pasparakis, Peter Vandenabeele
Feb 19, 2015·Nature Communications·Kate E LawlorJames E Vince
May 21, 2015·Nature Communications·Xiaodong MaYong Li
Feb 13, 2016·Annual Review of Biochemistry·Kim Newton, Gerard Manning
Sep 20, 2016·Cellular and Molecular Gastroenterology and Hepatology·Johanna LouhimoGeorge Perides
Dec 14, 2016·Annual Review of Pathology·Lorenzo GalluzziGuido Kroemer
Aug 26, 2017·Gut·Sven M van DijkUNKNOWN Dutch Pancreatitis Study Group
Sep 18, 2017·Gastroenterology·Anna S GukovskayaAida Habtezion
Nov 24, 2018·Nature Reviews. Neuroscience·Junying YuanDimitry Ofengeim
Dec 5, 2018·Trends in Biochemical Sciences·Emma J PetrieJames M Murphy
May 3, 2019·Proceedings of the National Academy of Sciences of the United States of America·Alexei DegterevJunying Yuan
Jun 18, 2019·The American Journal of Gastroenterology·Elaina VivianPaul Tarnasky
Aug 9, 2019·JCI Insight·Mary E ChoiAugustine M K Choi
Jul 10, 2020·Nature Reviews. Rheumatology·Holly AndertonJohn Silke
Sep 3, 2020·Nature Reviews. Molecular Cell Biology·Sammy BedouiAndreas Strasser
Sep 7, 2020·Lancet·Lotte BoxhoornMarc G Besselink

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Citations

Aug 7, 2021·Biochemical and Biophysical Research Communications·Qinhao ShenGuanghuai Yao

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