Molecular Mechanisms of Childhood Idiopathic Nephrotic Syndrome
Lay Abstract
Mechanisms of Childhood Nephrotic Syndrome Idiopathic nephrotic syndrome is the most common glomerular disorder in children. It occurs when there is sudden damage to the cells of the kidney’s filtering system. The result is leakage of protein from the blood into the urine and increased likelihood of progressing to more chronic forms of kidney disease into adulthood. When these filtering cells, called podocytes, are injured, they release small pieces of their outer cell layer that can be detected in the urine. These small pieces of the cell, known as extracellular vesicles, may provide an early warning of kidney injury and signs of ineffective treatment.
Our goal is to understand how these extracellular vesicles are produced and what cargo they contain during the disease process.
We will focus on two targets:
(1) a critical enzyme, known as NOX5, that produces highly volatile oxygen molecules in podocytes that are associated with cell damage, including extracellular vesicles; and
(2) these reactive oxygen molecules can damage key components of a cell including mitochondria, the energy factories of the cell, resulting in mitochondrial DNA release and packaged into extracellular vesicles. We will carry out this project using both animals models and human patient samples. Ultimately, this work could identify new targets for therapy aimed at curtailing kidney injury at the earliest stages of disease.
