Promising Research May Provide Key Clues to Kidney Development

July 17, 2008 — The kidney is one of the most underappreciated organs in the body. Most people are familiar with the kidney’s unglamorous but critical role of filtering the blood to remove waste, but the kidney also secretes hormones that are responsible for essential physiological functions such as red blood cell and bone production and the regulation of blood pressure.

Scientists have been studying kidney development through molecular genetics for the past two decades, with significant but scattered progress, according to Jing Yu, an assistant professor of cell biology at the University of Virginia.

Yu recently received a $50,000 grant from U.Va.'s Fund for Excellence in Science and Technology Distinguished Young Investigator program to further elucidate the complexities of kidney development.

A primary goal of Yu's research is to further explore renal development through the kidney's molecular beginnings. The number of nephrons — functional units of the kidney — that people have is determined during their embryonic development. Research has shown that nephrons are critical to a number of physiological processes, both in the kidney and beyond. People born with a lower number of nephrons, for example, are more prone to developing hypertension, or high blood pressure, said Yu. Thus, proper renal development is essential for renal physiology, and a more comprehensive understanding of the development of the kidney and its many functions could have significant health implications.

In addition, Yu's research is likely to have wider relevance. "The kidney has been used as a model for organogenesis — that means organ development — for over 50 years now," Yu said. "Its development employs many of the common mechanisms shared in other epithelial organ development. So by studying and understanding kidney development, we can also learn basic principles of how the lung develops, for example, or the pancreas."

Yu's newly funded project proposes a novel approach by focusing on the role of microRNA in kidney development. MicroRNAs are a newly identified family of molecules that have been implicated in the regulation of genes. Research has established that microRNAs are a key factor in major biological processes such as stem-cell renewal and oncogenesis — cancer formation. Yu's initial research suggests that microRNAs may also be important in regulating the development of the kidney.

Yu's lab employs mouse genetics for this research, applying a tissue-specific technique to remove a gene that activates microRNA functions in the kidney. In the absence of this gene, researchers can observe alterations in kidney organogenesis, which will allow them to connect microRNAs to specific aspects of kidney development. Since microRNAs may be involved in disease processes, Yu's research holds promise for the prevention and diagnosis of genetic disorders such as renal dysplasia, a major cause for end-stage renal failure in children, and polycystic kidney disease, which afflicts as many as 1 in 500 people.

"I think the importance of having this award is to set the stage for a long-term study that will be important for our understanding of kidney development," Yu said. "What we will study here not only will tell us the mechanisms of normal kidney development, but it will help us to understand the etiology of related renal anomalies."

The Fund for Excellence in Science and Technology Distinguished Young Investigator Grant Program is administered by U.Va.'s Office of the Vice President for Research and Graduate Studies and supports junior faculty research in the sciences, engineering, and medicine.

— By Melissa Maki