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Protein protects kidneys from damage caused by chronic renal disease and injury

ANN ARBOR, Mich. University of Michigan scientists have identified a new and unusual protein that reduces, in laboratory mice, kidney damage caused by chronic renal disease and acute toxic injuries.

Named KCP, for kielin/chordin-like protein, the new protein is the first of its kind found to directly enhance signals from bone morphogenetic proteins or BMPs, which are vital to the normal development and healthy functioning of the kidney.

"KCP is similar in structure to proteins like chordin, which suppress BMP signals during embryonic development," says Gregory R. Dressler, Ph.D., an associate professor of pathology in the U-M Medical School, who directed the research study. "But instead of suppressing the signal, KCP enhances it by strengthening interactions between the BMP protein and its receptor on kidney cells."

"In two different models of mice with renal injuries, we found that KCP activity was required to slow the progression of kidney disease," Dressler says. "Mice that couldn't secrete KCP protein were more susceptible to renal injuries, had higher mortality rates and showed more fibrosis and scarring than normal mice. Our data suggest that KCP could have the potential to be a therapeutic agent for fibrotic renal disease in humans."

Results of the study were published March 27 by Nature Medicine on its Advance Online Publication Web site.

Developmental biologists like Dressler have been studying bone morphogenetic proteins for decades, because they are so important to the regulation of embryonic development in mammals. BMPs aren't as familiar to clinical scientists, because only a handful of studies, conducted during the last six years, have examined the effects of BMPs on renal disease. BMP7, in particular, plays an essential role in kidney disease and development.

"When BMP7 binds to the type 1 receptor on a kidney epithelial cell, it triggers signaling proteins called Smads, which are inside the c
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28-Mar-2005


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