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Rong Li Lab identifies new role of inflammatory protein in PKD and a possible treatment

The Stowers Institute's Rong Li Lab has discovered that a protein previously shown to have a role in inflammation may also have a role in the formation of cysts in Autosomal Dominant Polycystic Kidney Disease (ADPKD) one of the most common life-threatening genetic diseases and has shown that a drug inhibiting the protein can slow the disease in mice.

The discovery was published in the advance online publication of Nature Medicine yesterday.

The team showed that a pro-inflammatory cytokine protein tumor necrosis factor-alpha (TNF-alpha) disrupts the localization of polycystin 2 the product of a gene mutated in ADPKD) to the plasma membrane and primary cilia in kidney epithelial cells, thus promoting the formation of cysts.

"The interaction between TNF-alpha and polycystin in the development of cysts is complicated," said Xiaogang Li, Ph.D., Senior Research Associate in the Rong Li Lab and first author on the paper. "We believe that this interaction could play a significant role in the transition from normal tubule development to the onset of Polycystic Kidney Disease (PKD) in individuals predisposed for the disease."

Additionally, the team found that the drug etanercept, an inhibitor of TNF-alpha currently used to treat rheumatoid arthritis and a number of other conditions, prevents the formation of cysts in the kidneys of mice with ADPKD.

"This discovery is especially exciting because it not only provides insight about the origins of ADPKD, but it also points us toward a drug that we believe shows promise in preventing the development of cysts," said Rong Li, Ph.D., Investigator and senior author on the publication. "Of course, additional research will be required to test these preliminary results in animal models, but the potential is interesting."

Currently, no treatments are available to prevent or delay the onset of cysts in people living with PKD. Dialysis and kidney transplants are often required as the disease progresses.


Contact: Marie Jennings
Stowers Institute for Medical Research

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