Navigation Links
UT Southwestern researchers probe kidney damage, protection in lupus
Date:4/20/2009

DALLAS April 21, 2009 Kidney damage associated with the autoimmune disease lupus is linked to a malfunction of immune cells that causes them to congregate in and attack the organs, researchers at UT Southwestern Medical Center have discovered in a mouse study.

In a separate study with an international team, the researchers also found that a certain set of genes appears to protect the kidneys from a different sort of immune attack in both mice and humans.

"These studies, taken together, uncover two important molecules that underlie the pathology of lupus, particularly kidney disease," said Dr. Edward Wakeland, chairman of immunology at UT Southwestern and co-senior author of the studies.

"In addition, they highlight a certain molecule as a potential target for treating this disease," he said.

In the first study, which appears in the April issue of The Journal of Immunology, the researchers examined several strains of mice that mimic human lupus. They found that immune cells in those mice overproduced a particular molecule called CXCR4. In fact, the mice had up to twice as much CXCR4 as their normal counterparts in several types of immune cells. The lupus-prone mice also had more immune-system cells in their kidneys, indicating that the inflammatory action of the immune cells might be causing the kidney damage.

The CXCR4 molecule was already known to play a role in creating various types of blood cells and also has been shown to be active in cancer and AIDS. Cells with CXCR4 on their surface are attracted to another molecule released by cells in various organs, so they migrate toward those organs, including the kidney.

When the researchers treated the lupus mice with a substance that blocks CXCR4, the symptoms of lupus significantly diminished; many symptoms of kidney failure were averted; and the mice lived longer. The increased lifespan was greater when treatment began at an early age.

"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 lead author and graduate student Andrew Wang; Dr. Anna-Marie Fairhurst, assistant instructor of immunology; Dr. Katalin Tus, instructor of immunology; former graduate student Srividya Subramanian; Dr. Yang Liu, postdoctoral researcher in internal medicine; Dr. Fangming Li, assistant professor of pediatrics; Dr. Peter Igarashi, professor of internal medicine; and Dr. Xin Zhou, professor of pathology. Researchers from the Universit Paris-Descartes and Chemokine Therapeutics, Canada, also participated.


'/>"/>

Contact: Aline McKenzie
aline.mckenzie@utsouthwestern.edu
214-648-3404
UT Southwestern Medical Center
Source:Eurekalert

Related biology news :

1. Diabetics on high-fiber diets might need extra calcium, report UT Southwestern researchers
2. Two UT Southwestern researchers awarded Sloan fellowships
3. UT Southwestern researchers identify molecule that helps the sleep-deprived to mentally rebound
4. UT Southwestern researchers disrupt biochemical system involved in cancer, degenerative disease
5. Natural brain substance blocks weight gain in mice, UT Southwestern researchers discover
6. UT Southwestern scientist honored among best in Texas research
7. UT Southwestern researchers identify gene linked to inherited form of fatal lung disease
8. Deranged calcium signaling contributes to neurological disorder, UT Southwestern researchers find
9. UT Southwestern researcher awarded Gates Foundation grant for novel vaccine development
10. RSV may hide in the lungs, lead to asthma, UT Southwestern researchers report
11. Waste from gut bacteria helps host control weight, UT Southwestern researchers report
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:4/17/2017)... 17, 2017 NXT-ID, Inc. (NASDAQ: NXTD ... filing of its 2016 Annual Report on Form 10-K on Thursday ... ... available in the Investor Relations section of the Company,s website at ... website at http://www.sec.gov . 2016 Year Highlights: ...
(Date:4/11/2017)... Research and Markets has announced the addition of the ... ... to grow at a CAGR of 30.37% during the period 2017-2021. ... been prepared based on an in-depth market analysis with inputs from ... prospects over the coming years. The report also includes a discussion ...
(Date:4/5/2017)...  The Allen Institute for Cell Science today announces ... portal and dynamic digital window into the human cell. ... application of deep learning to create predictive models of ... a growing suite of powerful tools. The Allen Cell ... publicly available resources created and shared by the Allen ...
Breaking Biology News(10 mins):
(Date:9/14/2017)... ... September 14, 2017 , ... DrugDev ... biotech at the third annual DrugDev Summit, November 7-8, 2017 in Philadelphia, PA. ... most progressive clinical research leaders for best practice case studies, keynote presentations, lively ...
(Date:9/14/2017)... ... September 14, 2017 , ... AxioMed is pleased ... Australia. Dr. Steven Yang completed the procedure on a 35-year-old female patient suffering ... lumbar disc at level L5-S1. The patient failed conservative treatments prior to undergoing ...
(Date:9/14/2017)... , ... September 14, 2017 , ... ... Management and exploratory analytics solutions, today announced that its Anzo Smart Data Lake ... year, KMWorld’s list includes technologies and solutions that help organizations succeed in surpassing ...
(Date:9/12/2017)... ... September 12, 2017 , ... PhysIQ, a ... platform for ambulatory patient monitoring and clinical trial support, earned DPharm Idol 2017 ... in Boston. , Launched in 2005, PhysIQ leverages artificial intelligence (AI) to ...
Breaking Biology Technology: