Navigation Links
Receptor protein appears to be key in breakdown of kidney filtration
Date:12/19/2007

Massachusetts General Hospital (MGH) researchers have identified a new molecular pathway that appears to be involved in urinary protein loss (proteinuria). This early-stage kidney disease affects 100 million people around the world and is caused by a breakdown in the kidneys filtering structures. Blocking this pathway could be a treatment for the condition and might significantly slow the process of kidney failure. The research teams findings will appear in Nature Medicine and have been released online.

Weve identified a mechanism that underlies common forms of urinary protein loss and have data showing that it is operative in humans and in animal models of proteinuria, says Jochen Reiser, MD, PhD, director of the Program in Glomerular Disease at the MGH Renal Division, the studys senior author.

Targeting this mechanism with antibodies or small molecule compounds can prevent or decrease proteinuria in animals, which may represent a novel therapy for kidney diseases such as diabetic nephropathy and focal segmental glomerulosclerosis, adds Changli Wei, MD, PhD, first author of the article.

The kidneys filtering activity takes place in clusters of blood vessels called glomeruli. Within those structures, extensions from cells called podocytes wrap around blood vessels. Tiny slits in the podocytes filter out excess water and waste materials, keeping larger proteins and blood cells inside the vessels. In several types of kidney disease, podocytes shrink and lose their structure, which compromises the filtering slits, allowing protein molecules to leak into the urine.

In the current study, the authors establish for the first time that the podocyte extensions called foot processes are capable of motion. In some kidney disorders, excess motility of these structures may be involved in the breakdown of podocytes that leads to proteinuria. To investigate this possibility, the researchers focused their attention on molecules known to be associated with cellular motility in a number of situations. One of these is the urokinase receptor (uPAR), which is known to be involved in wound healing and inflammation, as well as tumor invasion and metastasis.

Reisers team found that uPAR expression is elevated in glomerular cells of patients with several forms of kidney disease, compared with healthy controls. Animal studies showed that uPAR is expressed in all glomerular cells, yet it does not appear to be required for normal kidney function, since renal function is not compromised in mice lacking the gene for the protein. When the uPAR-knockout mice were treated with a substance that usually induces proteinuria, they did not develop the condition, suggesting that the receptors presence is required for the breakdown of podocyte structure.

After the gene encoding uPAR was introduced into podocytes of the knockout mice, they began expressing the receptor within 24 hours and became susceptible to the proteinuria-inducing treatment. The researchers then showed that uPAR can associate with and activate another receptor protein, alphavbeta3 integrin, leading to podocyte motility. Blocking this step in the uPAR-controlled pathway could reduce or prevent the development of proteinuria in mice. Such an agent is currently in phase II clinical trials for the brain tumor glioblastoma and may become available for use in patients with proteinuria.

Further investigation is required to discover how the uPAR pathway may interact with other molecular mechanisms involved in proteinuria, including the activity of an enzyme called cathepsin L, reported earlier this year by members of the same research team. We are working now in two directions to better understand the relationship between uPAR and cathepsin L and to conduct a clinical trial with small molecules blocking uPAR or alphavbeta3 integrin, says Reiser, an assistant professor of Medicine at Harvard Medical School. We hope this could be the first step towards a cell-specific treatment of proteinuric kidney diseases that would add on to the great success of standard, but non-cell-specific interventions for these diseases.


'/>"/>

Contact: Sue McGreevey
smcgreevey@partners.org
617-724-2764
Massachusetts General Hospital
Source:Eurekalert

Related medicine news :

1. Investigational Agent Targeting Metabotropic Glutamate 2/3 Receptors Demonstrates Antipsychotic Activity in Humans, Study in Nature Medicine Finds
2. Low level of neuronal receptor linked to mild cognitive impairment and Alzheimers disease
3. Pathway Diagnostics Announces Commercial Availability of SensiTrop(TM) HIV Co-receptor Tropism Assay
4. Pharmacopeia Acquires Selective Androgen Receptor Modulator (SARM) Program from Bristol-Myers Squibb
5. Food restriction increases dopamine receptor levels in obese rats
6. Quest Diagnostics Licenses Technology Underlying SensiTrop(TM) HIV Co-Receptor Tropism Test from Pathway Diagnostics
7. Abbott Researchers Target Neuronal Nicotinic Receptors for Treatment of Pain and Cognition
8. Exelixis to Receive Milestone Payment From Bristol-Myers Squibb for Achievement of Liver X Receptor Agonist Development Milestone
9. Draining away brains toxic protein to stop Alzheimers
10. Penn study finds pro-death proteins required to regulate healthy immune function
11. New prion protein discovered by Canadian scientists may offer insight into mad cow disease
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:10/13/2017)... Pekin, IL (PRWEB) , ... October 13, 2017 ... ... Foundation, which established the certification process to promote standards of excellence for the ... iaedp™ Symposium, scheduled for March 22 – 25, 2018 in Orlando, Florida at ...
(Date:10/13/2017)... , ... October 13, 2017 , ... Lori R. Somekh, ... member of ElderCounsel, a national organization of elder law and special needs planning attorneys. ... and rules. It also provides a forum to network with elder law attorneys nationwide,” ...
(Date:10/13/2017)... ... October 13, 2017 , ... The Visiting Nurse Association (VNA) ... a collection of specialty vendors and unique items from across the nation, this holiday-themed ... and wellness services offered by the VNA. The boutique will be open Saturday, ...
(Date:10/13/2017)... ... ... Yisrayl Hawkins, Pastor and Overseer at The House of Yahweh, has released a ... books in the Holy Scriptures, Revelation. The Book of Revelation paints a picture of ... have tossed it off as mere rubbish, but Yisrayl Hawkins says that is because ...
(Date:10/13/2017)... ... October 13, 2017 , ... “The Journey: From the ... danger possible to save lost souls in the Philippines. “The Journey: From the Mountains ... a dedicated teacher of the Bible. She has taught all ages and currently teaches ...
Breaking Medicine News(10 mins):
(Date:10/2/2017)... 2017  AllianceRx Walgreens Prime, the combined central specialty ... pharmacy benefit manager Prime Therapeutics LLC (Prime), today officially ... the unveiling of new signage at its headquarters in ... at a few other company-owned facilities across the country. ... some of whom will begin to see the AllianceRx ...
(Date:9/28/2017)... , Sept. 28, 2017 Hill-Rom Holdings, ... 2017 earnings conference call and webcast on Friday, November ... a.m. (EDT) and ending at approximately 8:30 a.m. (CDT) ... discussing the company,s 2017 financial performance and guidance for ... opportunities, initiatives to enhance operational performance, and long-range financial ...
(Date:9/27/2017)... Sept. 27, 2017  DarioHealth Corp. (NASDAQ: DRIO), a leading global digital ... its MyDario product is expected to appear on The Dr. Oz Show ... Oz Show airs in your area: http://www.doctoroz.com/page/where-watch-dr-oz-show ... The nine-time Emmy award-winning, The Dr. Oz Show kicked off ... The segment features ...
Breaking Medicine Technology: