Featured Research

from universities, journals, and other organizations

Blocking signal-transmitting cellular pores may prevent kidney damage

Date:
November 15, 2013
Source:
Massachusetts General Hospital
Summary:
A group of 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.

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.


Story Source:

The above story is based on materials provided by Massachusetts General Hospital. Note: Materials may be edited for content and length.


Journal Reference:

  1. Thomas Schaldecker, Sookyung Kim, Constantine Tarabanis, Dequan Tian, Samy Hakroush, Philip Castonguay, Wooin Ahn, Hanna Wallentin, Hans Heid, Corey R. Hopkins, Craig W. Lindsley, Antonio Riccio, Lisa Buvall, Astrid Weins, Anna Greka. Inhibition of the TRPC5 ion channel protects the kidney filter. Journal of Clinical Investigation, 2013; DOI: 10.1172/JCI71165

Cite This Page:

Massachusetts General Hospital. "Blocking signal-transmitting cellular pores may prevent kidney damage." ScienceDaily. ScienceDaily, 15 November 2013. <www.sciencedaily.com/releases/2013/11/131115130157.htm>.
Massachusetts General Hospital. (2013, November 15). Blocking signal-transmitting cellular pores may prevent kidney damage. ScienceDaily. Retrieved August 22, 2014 from www.sciencedaily.com/releases/2013/11/131115130157.htm
Massachusetts General Hospital. "Blocking signal-transmitting cellular pores may prevent kidney damage." ScienceDaily. www.sciencedaily.com/releases/2013/11/131115130157.htm (accessed August 22, 2014).

Share This




More Health & Medicine News

Friday, August 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Drug Used To Treat 'Ebola's Cousin' Shows Promise

Drug Used To Treat 'Ebola's Cousin' Shows Promise

Newsy (Aug. 21, 2014) An experimental drug used to treat Marburg virus in rhesus monkeys could give new insight into a similar treatment for Ebola. Video provided by Newsy
Powered by NewsLook.com
Cadavers, a Teen, and a Medical School Dream

Cadavers, a Teen, and a Medical School Dream

AP (Aug. 21, 2014) Contains graphic content. He's only 17. But Johntrell Bowles has wanted to be a doctor from a young age, despite the odds against him. He was recently the youngest participant in a cadaver program at the Indiana University NW medical school. (Aug. 21) Video provided by AP
Powered by NewsLook.com
American Ebola Patients Released: What Cured Them?

American Ebola Patients Released: What Cured Them?

Newsy (Aug. 21, 2014) It's unclear whether the American Ebola patients' recoveries can be attributed to an experimental drug or early detection and good medical care. Video provided by Newsy
Powered by NewsLook.com
Lost Brain Cells To Blame For Sleep Problems Among Seniors

Lost Brain Cells To Blame For Sleep Problems Among Seniors

Newsy (Aug. 21, 2014) According to a new study, elderly people might have trouble sleeping because of the loss of a certain group of neurons in the brain. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins