MicroRNA offers clue to treating diabetic kidney problems

A small piece of genetic material called microRNA-29c plays a major role in the development of kidney diseases related to diabetes, said researchers from Baylor College of Medicine in a recent report in the Journal of Biological Chemistry.

In a report that demonstrates the effect of this microRNA both in the laboratory and in animals, Dr. Farhad R. Danesh, associate professor of medicine – nephrology and pharmacology at BCM, and his colleagues show that microRNA-29c targets a particular gene called Sprouty homolog 1, reducing its expression. The gene Sprouty homolog 1 plays an important role in kidney development.

"Targeting the microRNA-29c in vivo in an animal model of diabetes can ameliorate the progression of kidney disease," said Danesh.

It is one of the first times that researchers have successfully blocked the action of a microRNA in live animals and treated their disease.

"By modulating the microRNA, we have modulated the disease process," he said. "The beauty of blocking microRNAs is that you do not have to knock out the gene completely. The microRNAs exert modest effect on their target genes, and if a gene is upregulated by about 20 to 25 percent, you can bring it down to normal physiological levels by inhibiting the microRNA."

MicroRNAs have gained prominence recently because these tiny pieces of genetic material can regulate the way in which genes are expressed. To find their microRNA of choice, Danesh and his colleagues screened kidney cells and tissues from diabetic animals for levels of microRNAs. They found microRNA-29c as one of only nine microRNAs consistently high in all samples. The fact that it targets Sprouty homolog 1 is also interesting since it was not previously known that Sprouty homolog 1 could play a role in diabetic kidney disease (nephropathy).

Danesh and his colleagues wanted to study how the microRNA worked in animals with diabetes. When the kidneys are affected in mice (or people) with diabetes, they have protein in their urine. However, when they gave diabetic mice a chemical that inhibited the microRNA-29c, the mice had a significant reduction of protein in their urine. In contrast, the untreated mice had higher levels of protein in the urine. When they followed the treated animals for 22 weeks, they found that they had significant improvement in their kidney function.

The finding is important because diabetic kidney disease is the leading cause of kidney failure in the United States and Western society. It is also one of the most significant long-term complications in terms of disability and death for individual patients with diabetes.

The next step is finding a drug that can inhibit the microRNA safely in people, he said.

Others who took part in this study include Drs. Jianyin Long, Yin Wang and Wenjian Wang, all of the Department of Medicine - Nephrology at BCM and Dr. Benny H.J. Chang, assistant professor of molecular and cellular biology at BCM.

Funding for this work came from the National Institute of Diabetes and Digestive and Kidney Diseases and the NIDDK-funded Diabetes and Endocrinology Research Center at Baylor College of Medicine.