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:12/9/2016)... (PRWEB) , ... December 09, 2016 , ... ... whiteboard display solutions, proudly announced today that a new solution for Emergency Departments ... fit in the tight space in Emergency Department examination rooms, and with a ...
(Date:12/8/2016)... Cambridge, MA (PRWEB) , ... December 08, 2016 ... ... the Workers Compensation Research Institute (WCRI) officially opened registration today for its ... Place Hotel in Boston, MA . , The theme of the conference is ...
(Date:12/8/2016)... ... December 08, 2016 , ... CURE Media Group, the nation’s leading digital ... aligned with Upstage Lung Cancer in efforts to combat lung cancer, announced CURE Media ... Jr said, “CURE Media Group is honored to team up with Upstage Lung Cancer ...
(Date:12/8/2016)... (PRWEB) , ... December 08, ... ... Presence Suite 10.2 version gives development continuity to its innovative Unified Instance ... channels management capacity. In addition, this new version optimizes the unattended auto-dialing ...
(Date:12/8/2016)... ... December 08, 2016 , ... Today’s patients are encouraged ... in mind, SIGVARIS has created a new line of anti-embolism stockings to help ... provide the benefits of graduated compression when transitioning from recovery to early rehabilitation. ...
Breaking Medicine News(10 mins):
(Date:12/8/2016)... 8, 2016 KEY FINDINGS ... of the market in 2016 and is expected to ... attributed to a large number of surgical procedures that ... largest share in the patient temperature management market.) Patient ... reducing loss of blood during surgeries, lowering the risks ...
(Date:12/8/2016)... Research and Markets has announced the addition ... Adhesion Type, Application, Usability - Forecast to 2025" report to ... , , ... poised to grow at a CAGR of around 3.2% from 2015 ... witnessing include advancements in extracellular microelectrode arrays and intracellular microelectrodes, research ...
(Date:12/8/2016)... 2016  Valeant Pharmaceuticals International, Inc. (NYSE: ... announced positive results from a Phase 3, multicenter ... safety and efficacy of IDP-118 (halobetasol propionate and ... Within the Phase 3 study ... psoriasis, IDP-118 showed statistical significance to vehicle with ...
Breaking Medicine Technology: