Navigation Links
Blocking signal-transmitting cellular pores may prevent damage to kidneys
Date:11/15/2013

One of the most devastating side effects of diabetes is kidney failure, and one of the earliest signs of kidney damage is a disruption of the organ's filtering capacity. Diabetes patients who develop kidney failure must go on dialysis, seriously limiting their quality of life and placing them at significantly increased risk of death. The incidence of kidney disease is increasing with rising rates of obesity-associated type 2 diabetes, but very little progress has been made towards protecting the kidney's filter barrier during the past 50 years.

Now a group of Massachusetts General Hospital (MGH) investigators has identified a molecule that plays a key role in the breakdown of the kidney filter, presenting a potential therapeutic target for stopping the damage before it becomes irreversible. Their report will appear in the December issue of the Journal of Clinical Investigation and is receiving early online release.

"Our study shows that blocking the ion channel TRPC5 may be a new treatment for diseases in which the kidney's filter barrier is damaged," says Anna Greka, MD, PhD, of the Division of Nephrology in the MGH Department of Medicine, who led the current study. "One in three Americans is at risk for developing chronic kidney disease from obesity, diabetes or high blood pressure; and kidney failure has been described as an emergent pandemic of our time."

TRPC5 is an ion channel, a pore in the cell membrane that transmits metabolic signals by allowing charged molecules in this case calcium to pass into or out of cells. Disrupted calcium signaling was suggested as a possible early event in damage to podocytes the cells that make up the kidney's filter barrier several decades ago, but the particular calcium channel that was involved had never been identified. Some families with a rare, inherited form of kidney disease were known to have activating mutations in a related calcium channel called TRPC6, which led Greka's team to investigate its role in kidney filtration. They were surprised to find that, in addition to TRPC6 channels, TRPC5 channels were also present in podocytes and that their activity was more damaging to the kidney filter, even in the absence of any mutations.

The current article describes a series of experiments by which Greka's team first confirmed the presence of TRPC5 channels in rodent podocytes; they then showed that animals in which TRPC5 expression was knocked out did not experience the type of kidney damage typically caused by a bacterial toxin or by a chemical known to damage podocytes. More detailed studies revealed that those damaging agents cause TRPC5 channels to open in podocytes, admitting excess calcium which causes the cytoskeleton the cells' internal structural support system to collapse, breaking down the filter formed by podocytes.

The researchers went on to show that a recently identified TRPC5 inhibitor, called ML204 discovered in the lab of study co-author Craig Lindsley, PhD, of Vanderbilt University Medical Center blocked the inrush of calcium into podocytes, preventing cytoskeletal breakdown and the damage to the kidney's filtering function. This protective effect was seen not only in cells and tissues but also in living mice.

"Future work needs to focus on optimizing ML204 and other potential TRPC5 blockers to be more potent. But generally our intention is to fervently pursue TRPC5 inhibition as a possible new treatment for the kidney diseases affecting hundreds of millions of people worldwide," says Greka, who is an assistant professor of Medicine at Harvard Medical School.


'/>"/>

Contact: Mike Morrison
mdmorrison@partners.org
617-724-6425
Massachusetts General Hospital
Source:Eurekalert

Related medicine news :

1. Patients with aberrations in two genes respond better to drugs blocking a well-known cancer pathway
2. Moffitt researchers say effective immunotherapy for melanoma hinges on blocking suppressive factors
3. Spread of Cancer May be Reduced by Maximizing Melatonin by Blocking Blue Light Says Photonic Developments LLC
4. Researchers prevent cancer spread by blocking tissue scarring
5. Evidence supports blocking immune response to enhance viral therapy against solid tumors
6. Autism Speaks trailblazer study -- Blocking cell distress signals can ease autism symptoms
7. Study shows additional role for abiraterone in blocking tumor growth in CRPC
8. Mount Sinai Researchers Find that Blocking Sugar Intake May Reduce Cancer Risk or Progression in Obese and Diabetic People
9. Blocking key enzyme in cancer cells could lead to new therapy
10. RxISK Drug Safety Petition Asks AbbVie and InterMune to Stop Blocking Access to Drug Clinical Trial Data
11. Blocking the active site of thiolase
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:4/30/2016)... Indianapolis, Indiana (PRWEB) , ... April 30, 2016 , ... ... USA Wrestling as they go for gold in Rio. Under the care of ... including two golds! , In an unprecedented showing, Maximized Living is sending the largest ...
(Date:4/29/2016)... ... April 29, 2016 , ... ... the Accreditation Council for Graduate Medical Education (ACGME) that it has received accreditation ... the first accreditation of three residency programs that Memorial is currently pursuing, including ...
(Date:4/29/2016)... ... April 29, 2016 , ... ... and author of best seller "LOVE, MEDICINE and MIRACLES") addresses touchy topics related ... 2016 and podcasted thereafter . Dr. Bernie Siegel, author of a plethora ...
(Date:4/29/2016)... ... April 29, 2016 , ... Spine Team Texas, a ... proud to announce one of their physicians has been invited to be a featured ... ACOFP) Family Practice Review conference on April 30, 2016. , Dr. R. Scott ...
(Date:4/29/2016)... ... ... the deadliest type of skin cancer. Although only about 1 percent of skin cancer cases ... 10,000 people are expected to die of melanoma this year. The risk increases with age, ... most commonly diagnosed cancers in young women. A recent breakthrough in genetic studies may give ...
Breaking Medicine News(10 mins):
(Date:4/28/2016)... 2016 , Net Sales of $1.90 billion ... the prior year period, and an increase of 1.2% on ... EPS for the first quarter were $0.52 reported, a decrease ... an increase of 29.9% over the prior year period ... guidance for 2016 Zimmer Biomet Holdings, Inc. (NYSE ...
(Date:4/28/2016)... N.J. , April 28, 2016   Acsis ... today announced that leading IT market research and advisory ... " in the IDC MarketScape: Worldwide Pharmaceutical Track and ... 2016).  The report provides an assessment of the capabilities ... track and trace software market. Logo - ...
(Date:4/28/2016)... 28, 2016 New market ... is a report that provides an overview of ... pipelines by identifying new targets and MOAs to ... Profiles discussed in this H1 2016 Osteoarthritis Pipeline ... AbbVie Inc., Abiogen Pharma S.p.A., Ablynx NV, Achelios ...
Breaking Medicine Technology: