Cargando…

Cytoglobin expression in the hepatic stellate cell line HSC-T6 is regulated by extracellular matrix proteins dependent on FAK-signalling

BACKGROUND: Fibrosis is a physiological response to cellular injury in the liver and is mediated by the activation of hepatic stellate cells resulting in the replacement of hepatocytes with extracellular matrix comprised principally of collagen 1 to form a hepatic scar. Although the novel hexaco-ord...

Descripción completa

Detalles Bibliográficos
Autores principales: Stone, Louise Catherine, Thorne, Lorna Susan, Weston, Christopher John, Graham, Mark, Hodges, Nikolas John
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4546255/
https://www.ncbi.nlm.nih.gov/pubmed/26300973
http://dx.doi.org/10.1186/s13069-015-0032-y
_version_ 1782386888097660928
author Stone, Louise Catherine
Thorne, Lorna Susan
Weston, Christopher John
Graham, Mark
Hodges, Nikolas John
author_facet Stone, Louise Catherine
Thorne, Lorna Susan
Weston, Christopher John
Graham, Mark
Hodges, Nikolas John
author_sort Stone, Louise Catherine
collection PubMed
description BACKGROUND: Fibrosis is a physiological response to cellular injury in the liver and is mediated by the activation of hepatic stellate cells resulting in the replacement of hepatocytes with extracellular matrix comprised principally of collagen 1 to form a hepatic scar. Although the novel hexaco-ordinated globin cytoglobin was identified in activated hepatic stellate cells more than 10 years ago, its role in stellate cell biology and liver fibrosis remains enigmatic. RESULTS: In the current study, we investigated the role of different extracellular matrix proteins in stellate cell proliferation, activation (alpha smooth muscle actin expression and retinoic acid uptake) and cytoglobin expression. Our results demonstrate that cytoglobin expression is correlated with a more quiescent phenotype of stellate cells in culture and that cytoglobin is regulated by the extracellular matrix through integrin signalling dependent on activation of focal adhesion kinase. CONCLUSIONS: Although further studies are required, we provide evidence that cytoglobin is a negative regulator of stellate cell activation and therefore may represent a novel target for anti-fibrotic treatments in the future. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13069-015-0032-y) contains supplementary material, which is available to authorized users.
format Online
Article
Text
id pubmed-4546255
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-45462552015-08-23 Cytoglobin expression in the hepatic stellate cell line HSC-T6 is regulated by extracellular matrix proteins dependent on FAK-signalling Stone, Louise Catherine Thorne, Lorna Susan Weston, Christopher John Graham, Mark Hodges, Nikolas John Fibrogenesis Tissue Repair Research BACKGROUND: Fibrosis is a physiological response to cellular injury in the liver and is mediated by the activation of hepatic stellate cells resulting in the replacement of hepatocytes with extracellular matrix comprised principally of collagen 1 to form a hepatic scar. Although the novel hexaco-ordinated globin cytoglobin was identified in activated hepatic stellate cells more than 10 years ago, its role in stellate cell biology and liver fibrosis remains enigmatic. RESULTS: In the current study, we investigated the role of different extracellular matrix proteins in stellate cell proliferation, activation (alpha smooth muscle actin expression and retinoic acid uptake) and cytoglobin expression. Our results demonstrate that cytoglobin expression is correlated with a more quiescent phenotype of stellate cells in culture and that cytoglobin is regulated by the extracellular matrix through integrin signalling dependent on activation of focal adhesion kinase. CONCLUSIONS: Although further studies are required, we provide evidence that cytoglobin is a negative regulator of stellate cell activation and therefore may represent a novel target for anti-fibrotic treatments in the future. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13069-015-0032-y) contains supplementary material, which is available to authorized users. BioMed Central 2015-08-21 /pmc/articles/PMC4546255/ /pubmed/26300973 http://dx.doi.org/10.1186/s13069-015-0032-y Text en © Stone et al. 2015 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Stone, Louise Catherine
Thorne, Lorna Susan
Weston, Christopher John
Graham, Mark
Hodges, Nikolas John
Cytoglobin expression in the hepatic stellate cell line HSC-T6 is regulated by extracellular matrix proteins dependent on FAK-signalling
title Cytoglobin expression in the hepatic stellate cell line HSC-T6 is regulated by extracellular matrix proteins dependent on FAK-signalling
title_full Cytoglobin expression in the hepatic stellate cell line HSC-T6 is regulated by extracellular matrix proteins dependent on FAK-signalling
title_fullStr Cytoglobin expression in the hepatic stellate cell line HSC-T6 is regulated by extracellular matrix proteins dependent on FAK-signalling
title_full_unstemmed Cytoglobin expression in the hepatic stellate cell line HSC-T6 is regulated by extracellular matrix proteins dependent on FAK-signalling
title_short Cytoglobin expression in the hepatic stellate cell line HSC-T6 is regulated by extracellular matrix proteins dependent on FAK-signalling
title_sort cytoglobin expression in the hepatic stellate cell line hsc-t6 is regulated by extracellular matrix proteins dependent on fak-signalling
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4546255/
https://www.ncbi.nlm.nih.gov/pubmed/26300973
http://dx.doi.org/10.1186/s13069-015-0032-y
work_keys_str_mv AT stonelouisecatherine cytoglobinexpressioninthehepaticstellatecelllinehsct6isregulatedbyextracellularmatrixproteinsdependentonfaksignalling
AT thornelornasusan cytoglobinexpressioninthehepaticstellatecelllinehsct6isregulatedbyextracellularmatrixproteinsdependentonfaksignalling
AT westonchristopherjohn cytoglobinexpressioninthehepaticstellatecelllinehsct6isregulatedbyextracellularmatrixproteinsdependentonfaksignalling
AT grahammark cytoglobinexpressioninthehepaticstellatecelllinehsct6isregulatedbyextracellularmatrixproteinsdependentonfaksignalling
AT hodgesnikolasjohn cytoglobinexpressioninthehepaticstellatecelllinehsct6isregulatedbyextracellularmatrixproteinsdependentonfaksignalling