March 13, 2012

Researchers Find Key Protein For Kidney Disease

A group of researchers from Mount Sinai School of Medicine have identified a key regulator protein that plays a role in kidney fibrosis. Kidney fibrosis, or renal fibrosis, is a condition that ultimately leads to kidney failure. This research could be a potential relief for the millions of Americans affected by kidney failure.

The Mount Sinai research team posted their findings in the March 11 issue of Nature Medicine.

John Cijiang He, MD, PhD, Professor of Nephrology and Pharmacology and Systems Therapeutics; and Avi Ma´ayan, PhD, Assistant Professor of Pharmacology and Systems Therapeutics at Mount Sinai School of Medicine led the research team as they studied three models of kidney fibrosis in mice. The first group of mice had HIV viral proteins incorporated into their genome. The second group of mice had been injected with a high dose of folic acid. Finally, in the third group of mice, kidney filtration was blocked in one kidney. Each of these three models represent factors that cause kidney fibrosis.

By using the genetic material of the mice studied in the models and comparing it against the genetic material of mice who did not have the disease, the scientists were able to find a protein kinase that was more highly active in the mice models with kidney fibrosis.

With the aid of new technology, computational systems biology algorithms, and new software called “Expression2Kinases” (developed by the Ma´ayan Laboratory at Mount Sinai), the team analyzed the experiment´s results. The protein kinase HIPK2 was highly active in the mice with kidney fibrosis. HIPK2 leads to fibrosis by regulating the way genes are expressed. Doctors He and Ma´ayan were able to pinpoint this kinase by eliminating it from the genetic material. Once removed, cases of fibrosis decreased and the overall condition of the mice improved.

With this target now discovered, scientists and doctors like He and Ma´ayan can begin to tailor their treatments of people experiencing kidney failure. According to Dr. He, this is only the beginning of their research: “Our findings have important implications for people with kidney diseases, patients I treat every day,” said Dr He. “Protein kinases like HIPK2 are highly effective therapeutic targets. We look forward to exploring this further.”

This research benefitted greatly from the advances of medical technology and computational biology. Had the team used the standard methods of examining gene expression changes, they may have missed the regulator protein HIPK2. With this research and the newly discovered target, Mount Sinai scientists can now work to develop new drugs that inhibit the activity of HIPK2.

“This study is an important example of the translational research we are doing at Mount Sinai,” said Dr. Ma´ayan said in the press release for the study. “Using algorithms and software developed here, we worked with Dr. He, who is a kidney disease physician and scientist, to better understand what causes kidney fibrosis, and we are now one step closer to finding a therapeutic solution to a complex disease that affects millions of Americans.”


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