The Role Of Vasoactive Hormones In The Pathogenesis Of Hepatic Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$271,320.00
Summary
One of the most important consequences of chronic liver disease is the development of progressive liver fibrosis or scarring. This process is responsible for many of the life-threatening complications of liver disease, however, the mechanisms responsible are not completely understood and there are no established treatments. The aetiologies of cirrhosis, or scarring of the liver, are many and vary from viral hepatitis to inherited and autoimmune disorders. Regardless of the cause, it appears that ....One of the most important consequences of chronic liver disease is the development of progressive liver fibrosis or scarring. This process is responsible for many of the life-threatening complications of liver disease, however, the mechanisms responsible are not completely understood and there are no established treatments. The aetiologies of cirrhosis, or scarring of the liver, are many and vary from viral hepatitis to inherited and autoimmune disorders. Regardless of the cause, it appears that fibrosis develops down a common pathway leading to eventual cirrhosis. We will study the pathways that are thought to be involved in the stimulation of liver scarring, in particular, focusing on those that lead to its activation and perpetuation. It is hypothesised that these pathways will prove to be potential targets for the treatment and prevention of liver fibrosis.Read moreRead less
Airway Virus Infection, Protease-activated Receptors And Microvascular Permeability
Funder
National Health and Medical Research Council
Funding Amount
$421,527.00
Summary
Asthma is an inflammatory airway disease which kills about 800 Australians each year and otherwise afflicts millions of children and adults in all age groups. Respiratory tract viral infections trigger inflammation and asthma. We believe that this is caused by the loss of naturally protective, bronchodilator and anti-inflammatory substances such as prostaglandin E2 and increased production of asthma promoting substances such as endothelins. Both of these substances are made by the epithelial lin ....Asthma is an inflammatory airway disease which kills about 800 Australians each year and otherwise afflicts millions of children and adults in all age groups. Respiratory tract viral infections trigger inflammation and asthma. We believe that this is caused by the loss of naturally protective, bronchodilator and anti-inflammatory substances such as prostaglandin E2 and increased production of asthma promoting substances such as endothelins. Both of these substances are made by the epithelial lining cells of the bronchi where viruses grow. This project will assess the influence of respiratory tract virus infection on epithelial mechanisms for the production of PGE2 and endothelins. Respiratory viral infections are accompanied by airway inflammation and thus by elevated microvascular permeability and oedema which exacerbates obstruction in asthma. We will measure airway microvascular permeability changes during viral infection and assess the protective effect of stimulating protease-activated receptors which increases PGE2 production. The impact of the PAR system on the integrity of microvascular tissue and on epithelial endothelin production has not been previously investigated. In addition, the influence of respiratory tract viral infection on PAR function in this system is also unknown, but is potentially of great importance to our understanding of the behaviour and regulation of this natural bronchoprotective pathway. This work may lead to the use of novel PAR activators as combined bronchodilator-anti-inflammatory therapies in asthma.Read moreRead less