Fibrosis is a major mechanism driving chronic disease. A specific pathologic process (TGF/Smad signalling) plays an important role in scarring of the kidney and the heart; but our understanding of this process is limited. Our exciting new data has identified a chemical modification of a component of this scarring pathway (acetylation of Smad3), and this project seeks to determine whether this modification plays a pivotal role in regulating tissue scarring.
TGF-beta/Smad Signalling In Macrophage-mediated Renal Fibrosis.
Funder
National Health and Medical Research Council
Funding Amount
$683,739.00
Summary
Scarring of organs such as the kidney, lung or liver is a common mechanism leading to organ failure and death. We postulate that a type of white blood cell (the macrophage) can transition into the cell type (the fibroblast) responsible for making the excess collagen that leads to this scarring. If proven, this will be a major advance in our understanding of organ fibrosis and may identify new therapeutic approaches to currently intractable diseases.
Apoptosis Signal-regulating Kinase 1 (ASK1) Is A Major Pathway Of Stress-induced Renal Injury In Different Types Of Progressive Kidney Disease.
Funder
National Health and Medical Research Council
Funding Amount
$678,865.00
Summary
Oxidative stress plays an important role in progressive kidney disease. We have identified a stress-activated mechanism (the ASK1 pathway) through which oxidative stress may cause kidney disease. We will perform preclinical studies in models of different types of kidney disease with an ASK1 inhibitor drug and genetically modified mice. These studies will provide new insights into the pathogenesis of kidney disease and will determine the potential of ASK1 as therapeutic target in kidney disease.