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Basement membrane-like matrix inhibits proliferation and collagen synthesis by activated rat hepatic stellate cells: evidence for matrix-dependent deactivation of stellate cells

Gaca, M.D., Zhou, X., Issa, R., Kiriella, K., Iredale, J.P. and Benyon, R.C. (2003) Basement membrane-like matrix inhibits proliferation and collagen synthesis by activated rat hepatic stellate cells: evidence for matrix-dependent deactivation of stellate cells Matrix Biology, 22, (3), pp. 229-239. (doi:10.1016/S0945-053X(03)00017-9).

Record type: Article

Abstract

During liver fibrosis hepatic stellate cells become activated, transforming into proliferative myofibroblastic cells expressing type I collagen and ?-smooth muscle actin. They become the major producers of the fibrotic neomatrix in injured liver. This study examines if activated stellate cells are a committed phenotype, or whether they can become deactivated by extracellular matrix. Stellate cells isolated from normal rat liver proliferated and expressed mRNA for activation markers, ?-smooth muscle actin, type I procollagen and tissue inhibitor of metalloproteinases-1 following 5–7 day culture on plastic, but culture on Matrigel suppressed proliferation and mRNA expression. Activated stellate cells were recovered from plastic by trypsinisation and replated onto plastic, type I collagen films or Matrigel. Cells replated on plastic and type I collagen films proliferated and remained morphologically myofibroblastic, expressing ?-smooth muscle actin and type I procollagen. However, activated cells replated on Matrigel showed <30% of the proliferative rate of these cells, and this was associated with reduced cellular expression of proliferating cell nuclear antigen and phosphorylation of mitogen-activated protein kinase in response to serum. Activated HSC replated on Matrigel for 3–7 days progressively reduced their expression of mRNA for type I procollagen and ?-smooth muscle actin and both became undetectable after 7 days. We conclude that basement membrane-like matrix induces deactivation of stellate cells. Deactivation represents an important potential mechanism mediating recovery from liver fibrosis in vivo where type I collagen is removed from the liver and stellate cells might re-acquire contact with their normal basement membrane-like pericellular matrix.

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More information

Published date: 2003
Keywords: hepatic stellate cell, myofibroblast, basement membrane, liver fibrosis, collagen, Integrin

Identifiers

Local EPrints ID: 27066
URI: http://eprints.soton.ac.uk/id/eprint/27066
ISSN: 0945-053X
PURE UUID: fd6c9da8-4adc-419e-bc16-981669c90453

Catalogue record

Date deposited: 26 Apr 2006
Last modified: 17 Jul 2017 16:05

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Contributors

Author: M.D. Gaca
Author: X. Zhou
Author: R. Issa
Author: K. Kiriella
Author: J.P. Iredale
Author: R.C. Benyon

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