The bi-directional relationship between mast cells and hepatic stellate cells in liver fibrosis
The bi-directional relationship between mast cells and hepatic stellate cells in liver fibrosis
In this thesis I have examined the hypothesis that HSC and MC have a bi-directional relationship in liver fibrosis. This was examined by investigating a possible mechanism of MC recruitment within the fibrotic liver, and fibrogenic effects of MC mediators and their subsequent mechanism in HSC activation.
SCF expression in human and rat livers and HSC was investigated as a possible cytokine mediating the recruitment of MC to the fibrotic liver. by various techniques SCF mRNA and protein was detected in fibrotic livers and activated HSC. Addition of neutralising SCF antibodies to co-cultures of HSC and MC significantly inhibited M<C adherence to HSC.
As MC numbers have been reported to increase during liver fibrosis, MC subtypes were examined in human diseased livers and in rat CCl4 fibrotic livers by RT-PCR and immunohistochemistry in rat CCl4 fibrotic livers. In human livers MCT and MCTC were found in normal and fibrotic livers, whilst MMC and CTMC were found in rat normal and fibrotic livers. Immunohistochemistry illustrated MC hyperplasia in fibrotic rat livers within the portal tracts and fibrotic septae. The possible mitogenic effects of MC mediators on HSC were examined.
To conclude, these results suggest that HSC may recruit MC to the fibrotic liver by the synthesis of SCF, in turn MC may upregulate HSC activation by tryptase stimulation mediated by PAR-2. These findings may contribute to future studies involved in designing potential therapies to be used in controlling and possibly preventing liver fibrosis. With the recent discovery of PAR-2, and the induction of collagen synthesis by tryptase and SLIGRL possibly mediated by PAR-2, this may be an attractive target for future drug development.
University of Southampton
Gaça, Marianna Danuta Aleksandria
2016d161-604f-4105-82f1-80330c097edc
2000
Gaça, Marianna Danuta Aleksandria
2016d161-604f-4105-82f1-80330c097edc
Gaça, Marianna Danuta Aleksandria
(2000)
The bi-directional relationship between mast cells and hepatic stellate cells in liver fibrosis.
University of Southampton, Doctoral Thesis.
Record type:
Thesis
(Doctoral)
Abstract
In this thesis I have examined the hypothesis that HSC and MC have a bi-directional relationship in liver fibrosis. This was examined by investigating a possible mechanism of MC recruitment within the fibrotic liver, and fibrogenic effects of MC mediators and their subsequent mechanism in HSC activation.
SCF expression in human and rat livers and HSC was investigated as a possible cytokine mediating the recruitment of MC to the fibrotic liver. by various techniques SCF mRNA and protein was detected in fibrotic livers and activated HSC. Addition of neutralising SCF antibodies to co-cultures of HSC and MC significantly inhibited M<C adherence to HSC.
As MC numbers have been reported to increase during liver fibrosis, MC subtypes were examined in human diseased livers and in rat CCl4 fibrotic livers by RT-PCR and immunohistochemistry in rat CCl4 fibrotic livers. In human livers MCT and MCTC were found in normal and fibrotic livers, whilst MMC and CTMC were found in rat normal and fibrotic livers. Immunohistochemistry illustrated MC hyperplasia in fibrotic rat livers within the portal tracts and fibrotic septae. The possible mitogenic effects of MC mediators on HSC were examined.
To conclude, these results suggest that HSC may recruit MC to the fibrotic liver by the synthesis of SCF, in turn MC may upregulate HSC activation by tryptase stimulation mediated by PAR-2. These findings may contribute to future studies involved in designing potential therapies to be used in controlling and possibly preventing liver fibrosis. With the recent discovery of PAR-2, and the induction of collagen synthesis by tryptase and SLIGRL possibly mediated by PAR-2, this may be an attractive target for future drug development.
Text
750419.pdf
- Version of Record
More information
Published date: 2000
Identifiers
Local EPrints ID: 464129
URI: http://eprints.soton.ac.uk/id/eprint/464129
PURE UUID: 156359bc-357c-4777-9500-4107d756ed57
Catalogue record
Date deposited: 04 Jul 2022 21:19
Last modified: 16 Mar 2024 19:16
Export record
Contributors
Author:
Marianna Danuta Aleksandria Gaça
Download statistics
Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.
View more statistics