UT Southwestern researchers probe kidney damage, protectio... (p This study indicates that drugs acting...)

UT Southwestern researchers probe kidney damage, protection in lupus

Date:4/20/2009

p>"This study indicates that drugs acting against CXCR4 might become useful therapies," said Dr. Chandra Mohan, professor of internal medicine and co-senior author of the studies.

In the second study, published in the April issue of The Journal of Clinical Investigation, the researchers found that some members of a family of genes called kallikreins offered a degree of protection in both mice and humans against a type of kidney damage caused by a different mechanism.

For this mouse study, the researchers administered antibodies that attack a part of the kidney called the glomerular basement membrane, the portion of the organ that performs its main function of filtering wastes from blood. They then looked for genes that turned on or off in response to the antibody assault.

Nine forms of the kallikrein, or klk, gene became more active, resulting in a two- to sixfold increase in the proteins encoded by the genes in normal mouse strains, compared with lupus-prone strains. When some mice were given substances that block the action of kallikrein proteins, they showed more severe symptoms of lupus, suggesting that kallikreins protect against renal disease.

The researchers also studied 340 German patients with systemic lupus, matched with 400 healthy control subjects. The patients with lupus and kidney damage had klk genes that were different from those in the healthy patients. Similar findings were noted in a larger, more varied group of patients from Europe, the United States and Korea.

"All humans have Klk genes, but our findings show that some of us have a particular version that increases our risk for systemic lupus," Dr. Wakeland said.

Future research will examine the mechanisms by which CXCR4 and klk genes might be aberrantly regulated in lupus and how they could be therapeutically targeted in human lupus, the researchers said.

Other UT Southwestern researchers involved in the first study were
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Contact: Aline McKenzie
aline.mckenzie@utsouthwestern.edu
214-648-3404
UT Southwestern Medical Center
Source:Eurekalert

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UT Southwestern researchers probe kidney damage, protectio...(p This study indicates that drugs acting...)