Cell Connections

John Bissler, MD, Le Bonheur chief of Pediatric Nephrology and director of the Tuberous Sclerosis Center of Excellence, recently published research in Biology investigating the cellular-level dynamics that lead to polycystic kidney disease (PKD) when the Pkd1 gene or the Tsc2 gene is deleted.

The results showed that deletions of either gene increased the production of extracellular vesicles (EVs), particles that provide communication between cells, which appear to recruit genetically unaltered cells to participate in the development of kidney cysts. In addition, deletion of either the Pkd1 or Tsc2 gene caused kidney cells to take up more EVs and hold onto the EVs for a longer period of time. Researchers hope that further understanding of EVs’ impact on PKD will provide an avenue for new therapies.

Patient with stethoscope listens to doctor's chest

Le Bonheur Chief of Nephrology and Director of the Tuberous Sclerosis Center of Excellence, John Bissler, MD

“Patients with PKD and tuberous sclerosis complex (TSC) are born with typical kidneys, but quickly develop cysts causing a premature loss of kidney function,” said Bissler. “The more we understand how EVs are involved in the development of PKD, the more potential we have for early intervention to preserve kidney function.”

Results also showed that primary cilia, structures on the surface of cells that act as antennae or sensors, play a large role in transmitting and receiving EVs. When researchers deleted the Pkd1 gene and the gene responsible for the protein that builds cilia, EV production was lowered and PKD was less severe.

Other results included:

All of these results provide insight into the cellular-level mechanisms that lead to PKD, particularly the role that EVs play in this process.

“Our study suggests the possibility that EV production rates, tissue half-life, target homing and cargo differences may be involved in the disease process,” said Bissler. “Additional studies can help us identify diagnostic and prognostic biomarkers and ultimately reveal novel therapies to reduce cystic disease.”

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