Regulation Of Tissue-type Plasminogen Activator Gene Expression In Endothelial Cells And In Transgenic Mice
Funder
National Health and Medical Research Council
Funding Amount
$244,009.00
Summary
Tissue-type plasminogen activator (t-PA) is an enzyme which plays an important role in the removal of blood clots from the circulation. One of the major sites of production of t-PA are endothelial cells which line the blood vessel wall. The rate of t-PA production is greatly influenced by factors released from other cells. One of these factors is tumour necrosis factor (TNF). The t-PA gene is switched off in endothelial cells exposed to TNF. One of the aims of this project is to understand how t ....Tissue-type plasminogen activator (t-PA) is an enzyme which plays an important role in the removal of blood clots from the circulation. One of the major sites of production of t-PA are endothelial cells which line the blood vessel wall. The rate of t-PA production is greatly influenced by factors released from other cells. One of these factors is tumour necrosis factor (TNF). The t-PA gene is switched off in endothelial cells exposed to TNF. One of the aims of this project is to understand how the t-PA gene is suppressed by TNF in human endothelial cells and in transgenic mice. The transgenic mice we have available express the regulatory region of the t-PA gene (called the gene promoter) connected to a reporter gene called LacZ. We will use these animals to visualise the expression pattern of LacZ expression under normal conditions and in mice treated with TNF. The results of these experiments will provide new information as to how the t-PA gene is controlled in cells and in the body.Read moreRead less
Osteoporosis is a pathological loss of bone that affects many Australians. It occurs because of an excessive release of calcium from bone that is caused by the overactivity of the cells that break down bone, osteoclasts. We have studied two genes that are involved in the way these cells work and by a close examination of the the way they are regulated we hope to understand how osteoclasts are derived and how their activity is controlled. In particular we will look at two newly dicovered osteocla ....Osteoporosis is a pathological loss of bone that affects many Australians. It occurs because of an excessive release of calcium from bone that is caused by the overactivity of the cells that break down bone, osteoclasts. We have studied two genes that are involved in the way these cells work and by a close examination of the the way they are regulated we hope to understand how osteoclasts are derived and how their activity is controlled. In particular we will look at two newly dicovered osteoclast regulators called PPAR-gamma and PPAR-delta. These offer the opportunity for the development in the future of new, alternative drugs for the treatment of osteoporosis.Read moreRead less