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{Cortes:2019:10.1002/hep.30193,
author = {Cortes, E and Lachowski, D and Rice, A and Chronopoulos, A and Robinson, B and Thorpe, S and Lee, DA and Possamai, LA and Wang, H and Pinato, DJ and Del, Río Hernández AE},
doi = {10.1002/hep.30193},
journal = {Hepatology},
pages = {785--802},
title = {Retinoic acid receptor-β is downregulated in hepatocellular carcinoma and cirrhosis and its expression inhibits myosin-driven activation and durotaxis in hepatic stellate cells},
url = {http://dx.doi.org/10.1002/hep.30193},
volume = {69},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Hepatic stellate cells (HSCs) are essential perisinusoidal cells in the healthy and diseased liver. HSCs modulate extracellular matrix (ECM) homeostasis when quiescent, but in liver fibrosis, HSCs become activated and promote excess deposition of ECM molecules and tissue stiffening via force generation and mechanosensing. In hepatocellular carcinoma (HCC), activated HSCs infiltrate the stroma and migrate to the tumor core to facilitate paracrine signalling with cancer cells. Since the function of HSCs is known to be modulated by retinoids, we investigated the expression profile of retinoic acid receptor beta (RAR-β) in cirrhotic and HCC patients, as well as the effects of RAR-β activation in HSCs. We found that RAR-β expression is significantly reduced in cirrhotic and HCC tissues. Using a comprehensive set of biophysical methods combined with cellular and molecular biology, we have elucidated the biomechanical mechanism by which all trans-retinoic acid (ATRA) promotes HSC deactivation via RAR-β-dependent transcriptional downregulation of myosin light chain 2 (MLC-2) expression. Furthermore, this also abrogated mechanically driven migration towards stiffer substrates. CONCLUSION: Targeting mechanotransduction in HSCs at the transcriptional level may offer new therapeutic options for a range of liver diseases. This article is protected by copyright. All rights reserved.
AU  - Cortes,E
AU  - Lachowski,D
AU  - Rice,A
AU  - Chronopoulos,A
AU  - Robinson,B
AU  - Thorpe,S
AU  - Lee,DA
AU  - Possamai,LA
AU  - Wang,H
AU  - Pinato,DJ
AU  - Del,Río Hernández AE
DO  - 10.1002/hep.30193
EP  - 802
PY  - 2019///
SN  - 0270-9139
SP  - 785
TI  - Retinoic acid receptor-β is downregulated in hepatocellular carcinoma and cirrhosis and its expression inhibits myosin-driven activation and durotaxis in hepatic stellate cells
T2  - Hepatology
UR  - http://dx.doi.org/10.1002/hep.30193
UR  - https://www.ncbi.nlm.nih.gov/pubmed/30055117
UR  - http://hdl.handle.net/10044/1/64632
VL  - 69
ER  -
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