Researchers in City of Hope’s Leslie & Susan Gonda (Goldschmied) Diabetes & Genetic Research Center have linked a common complication of diabetes to a new source. The discovery leads to greater understanding of diabetes-related kidney disease and may point to new methods of controlling it.

Rama Natarajan, left, and Mitsuo Kato found a link between gene silencing and diabetic kidney disease. (Photo by Darrin S. Joy)

Researchers led by Mitsuo Kato, Ph.D., assistant research professor, and Rama Natarajan, Ph.D., professor, both of the Department of Diabetes and Metabolic Diseases Research found new evidence that diabetic kidney disease may be boosted by a gene control mechanism called RNA silencing.

In RNA silencing, cells use small pieces of genetic material called microRNA, or miRNA, to turn genes off. Natarajan and her lab team have been actively studying the role of miRNAs in diabetes and its kidney complications.

The researchers studied a kind of kidney cell that, when grown under diabetic conditions such as a high-sugar environment, produce large amounts of collagen and other similar proteins. Normally, these proteins bind cells together to form tissues and organs, but in diabetes, they may damage tiny vessels and lead to kidney disease.

Scientists know that overproduction of collagen in diabetes patients is linked to two other proteins: transforming growth factor-beta 1, or TGF-beta, and Ybx1.

Ybx1 halts collagen production; TGF-beta accelerates it.

In the current research, Natarajan and her team sought to understand how TGF-beta boosts collagen production. They found it pushes the cell to produce a key miRNA that blocks Ybx1, essentially taking away the barrier to collagen creation.

“There is still a great deal of work to do, but with better understanding of this mechanism, we could develop factors to control the miRNA,” said Natarajan. This would restore Ybx1, which would in turn slow down the cells’ harmful overproduction of collagen and similar proteins — and potentially control diabetic kidney disease, she added.

Diabetes is the most common cause of kidney failure, accounting for nearly 44 percent of new cases, according to the National Institutes of Health (NIH). Nearly 24 million people in the U.S. have diabetes, and nearly 180,000 people are living with kidney failure as a result of diabetes.

The editorial board of the Journal of Biological Chemistry has selected the study as “Paper of the Week” for the October issue. It appeared online on Aug. 16.

Other City of Hope researchers on the study include lead author Mitsuo Kato, Ph.D., Lin Wang, Sumanth Putta, Mei Wang, Guangdong Sun, M.D., Linda Lanting, Ivan Todorov, Ph.D., John J. Rossi, Ph.D., Lidow Family Research Chair.