Matches in SemOpenAlex for { <https://semopenalex.org/work/W3155852347> ?p ?o ?g. }
- W3155852347 abstract "Apoptosis is characterized by profound morphological changes, but their physiological purpose is unknown. To characterize the role of apoptotic cell contraction, ROCK1 was rendered caspase non-cleavable (ROCK1nc) by mutating aspartate 1113, which revealed that ROCK1 cleavage was necessary for forceful contraction and membrane blebbing. When homozygous ROCK1nc mice were treated with the liver-selective apoptotic stimulus of diethylnitrosamine, ROCK1nc mice had more profound liver damage with greater neutrophil infiltration than wild-type mice. Inhibition of the damage-associated molecular pattern protein HMGB1 or signalling by its cognate receptor TLR4 lowered neutrophil infiltration and reduced liver damage. ROCK1nc mice also developed fewer diethylnitrosamine-induced hepatocellular carcinoma (HCC) tumours, while HMGB1 inhibition increased HCC tumour numbers. Thus, ROCK1 activation and consequent cell contraction are required to limit sterile inflammation and damage amplification following tissue-scale cell death. Additionally, these findings reveal a previously unappreciated role for acute sterile inflammation as an efficient tumour-suppressive mechanism." @default.
- W3155852347 created "2021-04-26" @default.
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- W3155852347 date "2021-04-19" @default.
- W3155852347 modified "2023-10-02" @default.
- W3155852347 title "Defective apoptotic cell contractility provokes sterile inflammation, leading to liver damage and tumour suppression" @default.
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- W3155852347 doi "https://doi.org/10.7554/elife.61983" @default.
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