MicroRNA gene cluster a new target for treatment of kidney disease

A nephrology-based investigation, which included (from left) Dr. Sachin Hajarnis, Darren Williams, and Dr. Vishal Patel, has uncovered a potential target for developing a polycystic kidney disease drug treatment.
A nephrology-based investigation, which included (from left) Dr. Sachin Hajarnis, Darren Williams, and Dr. Vishal Patel, has uncovered a potential target for developing a polycystic kidney disease drug treatment.

By Remekca Owens

A family of microRNAs previously linked to various types of cancer has been identified by UT Southwestern Medical Center researchers as a potential target for developing a polycystic kidney disease drug treatment.

The investigation, discovered using animal models, suggests that the microRNA cluster miR-17~92 influences the progression of polycystic kidney disease. The study’s findings were published in the June 25 edition of Proceedings of the National Academy of Sciences.

“We sought out new pathways that promote cyst growth in polycystic kidney disease. In doing that, we discovered that the miR-17~92 microRNA cluster is a regulator of kidney cyst growth and a potential therapeutic target in polycystic kidney disease,” said Dr. Vishal Patel, Assistant Professor of Nephrology and lead author of the study.

Polycystic kidney disease is the most common genetic cause of chronic kidney failure, affecting more than 600,000 people in America and 12.5 million worldwide. The disease causes cysts to develop in the kidneys and blocks the organs’ ability to filter waste products from the blood. This causes the kidneys to become enlarged and potentially fail. Cysts also may develop in other organs, particularly the liver.

Once the disease has progressed to end-stage – typically when those affected are in their 50s and 60s  – patients’ only treatment options are dialysis or a kidney transplant. There is no Food and Drug Administration-approved therapy currently available to slow the growth of cysts in patients with the disease.

UT Southwestern researchers used mouse models that mimic key aspects of human polycystic kidney disease to study the role of microRNAs. They found that levels of miR-17~92 were higher in mice with polycystic kidney disease. When miR-17~92 was artificially overexpressed in normal mice, they developed kidney cysts, whereas when miR-17~92 was inhibited in mice with polycystic kidney disease, the size of cysts decreased, and the animals’ survival improved.

“We will next test whether it is possible to design drugs to inhibit miR-17~92 and whether the administration of these drugs slows progression of polycystic kidney disease in animal models,” Dr. Patel said.

Other UT Southwestern researchers involved in the study were senior author Dr. Peter Igarashi, Chief of Nephrology; Darren Williams, a research assistant in Internal Medicine; Dr. Sachin Hajarnis, a senior research associate in Internal Medicine; and Ryan Hunter, a graduate fellow.

The study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases and its George M. O’Brien Kidney Research Core Center at UT Southwestern.

Dr. Igarashi holds the Robert Tucker Hayes Distinguished Chair in Nephrology, in Honor of Dr. Floyd C. Rector Jr.

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