Birth Weight, Adult Weight And Podocyte Depletion.
Funder
National Health and Medical Research Council
Funding Amount
$796,252.00
Summary
A major role of our kidneys is to filter our blood. A key cell type in our kidney filters is an octopus-shaped cell known as the podocyte. If we are not born with enough podocytes, or if the filters grow too large after birth due for example to excessive weight gain, the podocytes cannot adequately filter the blood, and this can lead to kidney disease. We will measure podocyte endowment at birth, and assess the effects of weight gain and loss after birth on podocyte features and kidney health.
Hyperplasia And Hypertrophy Of Airway Smooth Muscle In Asthma
Funder
National Health and Medical Research Council
Funding Amount
$286,250.00
Summary
Asthma is common in Australia with significant morbidity and it is the 6th Australian National Health Priority. Examination of the airways in asthma shows increased thickness of the airway wall (remodeling), and inflammation. Most long-term asthma treatment is currently focussed on treating inflammation. Since the contribution of smooth muscle to remodeling and excessive airway narrowing is crucial and may be largely independent of airway inflammation, new treatments aimed at the smooth muscle a ....Asthma is common in Australia with significant morbidity and it is the 6th Australian National Health Priority. Examination of the airways in asthma shows increased thickness of the airway wall (remodeling), and inflammation. Most long-term asthma treatment is currently focussed on treating inflammation. Since the contribution of smooth muscle to remodeling and excessive airway narrowing is crucial and may be largely independent of airway inflammation, new treatments aimed at the smooth muscle are needed. Treatments must be based on knowledge of the factors which result in more smooth muscle - hypertrophy (enlargement of cells), hyperplasia (more cells) or deposition of proteins (extracellular matrix) between the muscle cells. Matrix is produced by airway myofibroblasts which are more numerous in asthma. These various contributing factors have different signals that can be targeted for treatment, however, information regarding their relative importance is scant. We propose to examine cases of mild and severe asthma using archived tissue blocks in a multi-centre collaborative study using stereological techniques not previously applied to the airway in man. This study is important because it will: 1. Yield new data regarding the degree to which hyperplasia, hypertrophy and increased extracellular matrix vary in the airways; 2. Provide direction for the development of treatments of increased smooth muscle in asthma; 3. Provide relevance and direction to animal and tissue studies of airway smooth muscle; 4. Yield new information on the number of myofibroblasts in mild and severe asthma; 5. Yield new information on the effects of corticosteroids on smooth muscle, extracellular matrix and myofibroblasts in severe, fatal asthma, and 6. Relate increased smooth muscle to increased extracellular matrix, numbers of myofibroblasts and other airway wall dimensions including those close to the airway surface. These may be used to monitor airway pathology in asthma.Read moreRead less
RENAL VASCULAR HYPERTROPHY AND REMODELLING IN SHR: SYMPATHETIC NERVOUS SYSTEM AND IMPLICATIONS FOR HYPERTENSION
Funder
National Health and Medical Research Council
Funding Amount
$191,561.00
Summary
High blood pressure (hypertension) remains a major health problem for Australians. One in six Australians suffer from hypertension, with consequent increased risk of stroke and heart attack. Anti-hypertensive treatments are available, but must usually be taken for the rest of the patient's life and the cost to the taxpayer of anti-hypertensive drugs is greater than for any other health problem. Prevention of high blood pressure depends on identifying the initial cause - but we still do not know ....High blood pressure (hypertension) remains a major health problem for Australians. One in six Australians suffer from hypertension, with consequent increased risk of stroke and heart attack. Anti-hypertensive treatments are available, but must usually be taken for the rest of the patient's life and the cost to the taxpayer of anti-hypertensive drugs is greater than for any other health problem. Prevention of high blood pressure depends on identifying the initial cause - but we still do not know the cause in over 90% of hypertensive people. This project will study whether overactivity of the nerves to the blood vessels of the kidney might be the cause. There is evidence for this in humans, and in a strain of rats which develops high blood pressure (the spontaneously hypertensive rat). Our experiments will study these rats to see whether nerves affect the structure and function of the blood vessels of the kidney in ways that lead to increased blood pressure.Read moreRead less
Exploring The Physiological, Morphological And Molecular Bases Of Renal Developmental Programming.
Funder
National Health and Medical Research Council
Funding Amount
$422,264.00
Summary
Suboptimal fetal and neonatal development increases our risk of developing a range of diseases in adulthood. The concept that deleterious events during development can influence adult health is termed 'developmental programming'. Obtaining A Healthy Start to Life is a priority research goal of the Australian Government. The kidneys are particularly susceptible to developmental programming. This is in part because the functional units (nephrons) of the kidneys are all formed before birth in human ....Suboptimal fetal and neonatal development increases our risk of developing a range of diseases in adulthood. The concept that deleterious events during development can influence adult health is termed 'developmental programming'. Obtaining A Healthy Start to Life is a priority research goal of the Australian Government. The kidneys are particularly susceptible to developmental programming. This is in part because the functional units (nephrons) of the kidneys are all formed before birth in humans. Thus, if fetal development is suboptimal, babies are at risk of being born with a permanent nephron deficit, with functional and disease consequences. We have shown in male rats that the offspring of a maternal low protein diet have fewer nephrons and lower blood pressure than rats fed a normal diet. These rats display a striking sensitivity in adulthood to the feeding of a high salt diet. We will define the physiological and morphological bases of this sensitivity, and repeat these studies in females, as increasing evidence shows significant sex differences in developmental programming. Defining the molecular mechanisms of developmental programming is the greatest challenge for researchers in the field. We have recently completed the most comprehensive analysis to date of gene expression in the developing mouse kidney, and have shown for the first time that the mouse programmes kidney development. We will use the new techniques of genomics and bioinformatics to study the molecular mechanisms of kidney programming. This mechanistic data will provide an excellent hypothesis engine for future studies on the specific roles of these molecular pathways in developmental programming in all mammalian species.Read moreRead less