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Molecular mechanisms involved in the loss of TGFbeta repression of matrix metalloproteinase gene transcription during cellular senescence

Reference	SAG09958
Principal Investigator / Supervisor	Professor Dylan Richard Edwards
Co-Investigators / Co-Supervisors	Professor Ian Clark
Institution	University of East Anglia
Department	Biological Sciences
Funding type	Research
Value (£)	169,552
Status	Completed
Type	Research Grant
Start date	01/10/1998
End date	01/10/2001
Duration	36 months

Abstract

Increased production of ECM-degrading matrix metalloproteinases (MMPs) is involved in the deterioration of tissue architecture during ageing. By comparing the responses of cultured replicatively senescent and young human diploid fibroblasts to agents that control MMP expression, we have shown that old cells fail to repress PMA-induced MMP transcription in response to TGF- Beta. This proposal will study molecular mechanisms involved in this impaired response. We will determine 1) expression of TGF- Beta receptors on ageing versus young cells; 2) the functional status of intracellular pathways known to be involved in TGF-Beta signalling; 3) cis- acting regulatory elements that mediate TGF- Beta repression of MMP transcription, and 4) the identities of the transcription factors involved. These studies will provide new information on a major signalling pathway that has physiological relevance to the ageing process.

Summary

unavailable

Committee	Closed Committee - Genes & Developmental Biology (GDB)
Research Topics	X – not assigned to a current Research Topic
Research Priority	X – Research Priority information not available
Research Initiative	Initiative on Science of Ageing (SAG) [1998]
Funding Scheme	X – not Funded via a specific Funding Scheme

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