June 23, 2000 Ohio University scientists have identified genes that may be involved in protecting the kidneys of diabetics from damage, a first step in the development of a drug or therapy for millions of people who suffer from kidney failure as a result of the disease.
The research, presented June 22 at the Endocrine Society annual meeting in Toronto, pinpoints three genes that may play a role in diabetic kidney disease, which affects between 1.5 and 3 million Americans. To understand the roots of this common complication, scientists examined gene function in healthy and sick mice. Earlier studies at Ohio University's Edison Biotechnology Institute found a connection between growth hormone and diabetic kidney disease -- diabetic mice engineered without the growth hormone receptor didn't get kidney disease.
Researchers focused their studies on the genetic structure of these kidneys to find out why they had escaped damage. "We have to look at what genes growth hormone affects because you can't do away with growth hormone itself," said Karen Coschigano, lead author of the recent study. "We don't want to lose the good things that growth hormone does."
For this new study, researchers examined the damaged kidneys of diabetic mice, the healthy kidneys of normal mice and the healthy kidneys of diabetic mice lacking the growth hormone receptor. Scientists noticed that two genes at work in the third group were inactive in the normal mice and in the diabetic mice with kidney disease. And they identified a third gene that was inactive in the mice missing the growth hormone receptor – but active in the other two groups. The finding points to a possible genetic cause of the disease.
Knowing which genes are involved and how they work could be useful in therapy or diagnosis of kidney disease, Coschigano said. Scientists could activate protective genes, for example, or turn off the damage-causing gene.
"The overall idea would be to discover drugs that would regulate these genes," said John Kopchick, co-author of the study and Goll-Ohio Eminent Scholar and professor of molecular and cellular biology.
"Potentially, we could give the diabetic person a recombinant protein derived from the gene as a drug, and if it's early enough, reverse the kidney damage or halt the progression," Coschigano said.
The genes also could help doctors track the health of a diabetic's kidney. "Instead of actually looking at the kidney to see if it's becoming less damaged, we could look at the change in the gene expression," she said.
Kidney disease, which impacts between 10 percent and 21 percent of the 15.7 million Americans with diabetes, often results in kidney failure, according to the American Diabetic Association. Tiny blood vessels in the kidneys that filter waste, chemicals and excess water from the blood become damaged and leaky. When the filtration system breaks down, patients require dialysis or kidney transplants to survive.
Though the study was conducted on mice, Coschigano notes that there is human evidence of the connection between growth hormone and kidney damage. People with acromegaly, a rare disease in which the body produces too much growth hormone, may have a higher incidence of diabetic kidney damage, she said.
In future studies, scientists hope to confirm the genes' roles in kidney health and explore how growth hormone is involved in the process.
The study was funded in part by the Central Ohio Diabetes Association, the State of Ohio's Eminent Scholar Program and Sensus Drug Development Corporation. The Edison Biotechnology Institute is a biomedical genetics institute at Ohio University and part of the Ohio Department of Development's Thomas Edison Program. Kopchick holds an appointment in the College of Osteopathic Medicine.
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