Role Of Nuclear Receptors In Hepatic Injury And Fibrogenesis
Funder
National Health and Medical Research Council
Funding Amount
$443,520.00
Summary
Chronic liver disease is a major cause of death and ill health on a word-wide scale. Several common liver diseases, such as hepatitis B, hepatitis C and non-alcoholic steatohepatitis (fatty liver disease not due to alcohol), are capable of causing protracted liver damage. Irrespective of the cause of injury, the liver has a very narrow way of responding to chronic damage. The most important and insidious of these is hepatic fibrosis (scarring), which, along with liver regeneration, eventually le ....Chronic liver disease is a major cause of death and ill health on a word-wide scale. Several common liver diseases, such as hepatitis B, hepatitis C and non-alcoholic steatohepatitis (fatty liver disease not due to alcohol), are capable of causing protracted liver damage. Irrespective of the cause of injury, the liver has a very narrow way of responding to chronic damage. The most important and insidious of these is hepatic fibrosis (scarring), which, along with liver regeneration, eventually leads to cirrhosis if the injurious process is sufficiently intense and sustained. Liver cirrhosis is the precursor to several undesirable complications of liver disease, most notably primary liver cancer (also called hepatoma), liver failure and severe bleeding from the gut. Therefore, it is not surprising that effective strategies to control liver injury and prevent cirrhosis have been called the holy grail of liver research. To date the only therapies for substantially improving the outcome of patients with chronic liver disease are those that halt or remove the cause of injury. Unfortunately, in many cases it is still not possible to remove or effectively treat the cause of injury. Because of this there is intense interest in therapies that might favourably alter the response of the liver to injury and especially in those that may retard or inhibit scarring and prevent cirrhosis. Nuclear receptors are sensors that control many aspects of the body's metabolism, especially the metabolism of cholesterol and fat. Recently, our work and that of others has suggested that some nuclear receptors may play a vital role in how the liver responds to damage and whether the liver will the scar and move on to cirrhosis. Our experiments will determine if this is so, and which of the several nuclear receptors likely to be involved are the important ones. We will then extend these studies to see if drugs that activate these receptors will improve or prevent severe liver disease.Read moreRead less
The Alternate Renin Angiotensin System; A Novel Target For The Prevention And Treatment Of Liver Fibrosis And Portal Hypertension
Funder
National Health and Medical Research Council
Funding Amount
$693,950.00
Summary
Cirrhosis of the liver due to chronic hepatitis and other common liver diseases is now a major cause of illness and death in Australia. This project will examine how a hormone system called the renin angiotensin system contributes to the development of liver damage in these diseases. We will study whether drugs targeting this system can be used to reduce liver scarring and prevent the development of cirrhosis and its complications.
Tissue Ferritin Is A Damage-associated Molecular Pattern (DAMP) In Inflammasome-induced Inflammation Associated With Hepatic Stellate Cell Activation And Fibrogenesis In Chronic Liver Disease.
Funder
National Health and Medical Research Council
Funding Amount
$783,612.00
Summary
We have generated considerable evidence for a role for tissue ferritin as a mediator of inflammation associated with liver fibrosis (scarring) These highly novel and innovative studies will assist in identifying pathways involved in the proinflammatory phenotype of hepatic stellate cells (scar-forming cells in the liver) in chronic liver disease and thus will greatly aid in understanding how liver scarring occurs in chronic liver disease.
Cellular Cross-talk Between Liver Progenitor Cells And Hepatic Stellate Cells Is Required For Hepatic Fibrogenesis
Funder
National Health and Medical Research Council
Funding Amount
$618,517.00
Summary
Deloitte Access Economics data proposes the total economic burden of liver disease in Australia in 2012 was >$50 billion. This study will identify how the liver heals itself by inducing liver cell populations which interact to regenerate damaged liver tissue in chronic liver disease. This knowledge may lead to the development of novel therapeutic interventions for the treatment of liver scarring and liver cancer, and to assist in normal liver regeneration following chronic liver disease.