Imperial College London
Alternate

DrArmandoDel Rio Hernandez

Faculty of Engineering, Department of Bioengineering

Reader in Cellular and Molecular Mechanotransduction
 
 
 
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Contact

 

+44 (0)20 7594 5187a.del-rio-hernandez

 
 
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Location

 

308Bessemer BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Julian:2021:10.7554/eLife.61983,
author = {Julian, L and Naylor, G and Wickman, GR and Rath, N and Castino, G and Stevenson, D and Bryson, S and Munro, J and McGarry, L and Mullin, M and Rice, A and Hernandez, ADR and Olson, MF},
doi = {10.7554/eLife.61983},
journal = {eLife},
pages = {1--32},
title = {Defective apoptotic cell contractility provokes sterile inflammation, leading to liver damage and tumour suppression},
url = {http://dx.doi.org/10.7554/eLife.61983},
volume = {10},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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.
AU  - Julian,L
AU  - Naylor,G
AU  - Wickman,GR
AU  - Rath,N
AU  - Castino,G
AU  - Stevenson,D
AU  - Bryson,S
AU  - Munro,J
AU  - McGarry,L
AU  - Mullin,M
AU  - Rice,A
AU  - Hernandez,ADR
AU  - Olson,MF
DO  - 10.7554/eLife.61983
EP  - 32
PY  - 2021///
SN  - 2050-084X
SP  - 1
TI  - Defective apoptotic cell contractility provokes sterile inflammation, leading to liver damage and tumour suppression
T2  - eLife
UR  - http://dx.doi.org/10.7554/eLife.61983
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000646615600001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://elifesciences.org/articles/61983
UR  - http://hdl.handle.net/10044/1/92398
VL  - 10
ER  -
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