Imperial College London
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DrJoseCortes Lopez

Faculty of Engineering, Department of Bioengineering

 
 
 
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Contact

 

+44 (0)7944 338 144j.e.corteslopez Website

 
 
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Location

 

B-122Bessemer BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Lachowski:2019:10.1038/s41598-019-43759-6,
author = {Lachowski, D and Cortes, E and Rice, A and Pinato, D and Rombouts, K and Del, Rio Hernandez A},
doi = {10.1038/s41598-019-43759-6},
journal = {Scientific Reports},
title = {Matrix stiffness modulates the activity of MMP-9 and TIMP-1 in hepatic stellate cells to perpetuate fibrosis},
url = {http://dx.doi.org/10.1038/s41598-019-43759-6},
volume = {9},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Liver  fibrosis  is  characterised  by  a  dense  and  highly  cross-linked  extracellular  matrix  (ECM)  which  promotes progression of diseases such as hepatocellular carcinoma. The fibrotic microenvironment is characterised  by  an  increased  stiffness,  with  rigidity  associated  with  disease  progression.  External  stiffness  is  known  to  promote  hepatic  stellate  cell  (HSC)  activation  through  mechanotransduction,  leading  to  increased  secretion  of  ECM  components.  HSCs  are  key  effector  cells  which  maintain  the  composition of the ECM in health and disease, not only by regulating secretion of ECM proteins such as  collagen,  but  also  ECM-degrading  enzymes  called  matrix  metalloproteinases  (MMPs)  and  their  inhibitors  (TIMPs).  Uninhibited  MMPs  degrade  ECM  proteins  to  reduce  external  rigidity.  Using  fibronectin-coated  polyacrylamide  gels  to  alter  substrate  rigidity  without  altering  ligand  density,  we  show  that  fibrotic  rigidities  downregulate  MMP-9  expression  and  secretion,  and  also  upregulate  secretion  of  TIMP-1,  though  not  its  expression.  Using  tissue  immunofluorescence  studies,  we  also  report  that  the  expression  of  MMP-9  is  significantly  decreased  in  activated  HSCs  in  fibrotic  tissues  associated  with  hepatocellular  carcinoma.  This  suggests  the  presence  of  a  mechanical  network  that  allows HSCs to maintain a fibrotic ECM, with external rigidity providing feedback which affects MMP-9 and TIMP-1 secretion, which may become dysregulated in fibrosis.
AU  - Lachowski,D
AU  - Cortes,E
AU  - Rice,A
AU  - Pinato,D
AU  - Rombouts,K
AU  - Del,Rio Hernandez A
DO  - 10.1038/s41598-019-43759-6
PY  - 2019///
SN  - 2045-2322
TI  - Matrix stiffness modulates the activity of MMP-9 and TIMP-1 in hepatic stellate cells to perpetuate fibrosis
T2  - Scientific Reports
UR  - http://dx.doi.org/10.1038/s41598-019-43759-6
UR  - http://hdl.handle.net/10044/1/66463
VL  - 9
ER  -
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