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), 229-239. (doi:10.1016/S0945-053X(03)00017-9).
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Description/Abstract
During liver fibrosis hepatic stellate cells become activated, transforming into proliferative myofibroblastic cells expressing type I collagen and α-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, α-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 α-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 α-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.
| Item Type: | Article |
|---|---|
| ISSNs: | 0945-053X (print) |
| Related URLs: | |
| Keywords: | hepatic stellate cell, myofibroblast, basement membrane, liver fibrosis, collagen, Integrin |
| Subjects: | R Medicine > RB Pathology Q Science > QL Zoology Q Science > QH Natural history > QH301 Biology |
| Divisions: | University Structure - Pre August 2011 > School of Medicine > Infection, Inflammation and Repair |
| Item ID: | 27066 |
| Date Deposited: | 26 Apr 2006 |
| Last Modified: | 01 Jun 2011 02:03 |
| Contributors: | Gaca, M.D. (Author) Zhou, X. (Author) Issa, R. (Author) Kiriella, K. (Author) Iredale, J.P. (Author) Benyon, R.C. (Author) |
| Date: | 2003 |
| Status: | Published |
| Contact Email Address: | rcb@soton.ac.uk |
| URI: | http://eprints.soton.ac.uk/id/eprint/27066 |
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