Featured Research

from universities, journals, and other organizations

Research offers way to disrupt fibrosis

Date:
November 10, 2013
Source:
Saint Louis University Medical Center
Summary:
Scientists have identified a pathway that regulates fibrosis, suggesting a possible pharmacologic approach to treat patients with a broad range of fibrotic diseases.

A team of scientists that includes Saint Louis University researchers has identified a new way to intervene in the molecular and cellular cascade that causes fibrosis -- a condition where the body's natural process of forming scars for wound healing goes into overdrive and causes diseases. The findings, published in the advance online Nov. 10 issue of Nature Medicine, demonstrate a potential novel therapeutic approach to treat fibrotic diseases such as idiopathic pulmonary fibrosis and liver fibrosis.

The research targets a pathway that turns off the trigger for the major molecular mediator of fibrosis, a protein called Transforming Growth Factor (TGF) beta. This protein is normally present in the body in an inactive state and must be turned on to cause fibrosis. Once activated, TGF beta protein stimulates cells called myofibroblasts to produce excess collagen, which is a principle component of scars.

The researchers showed that removing a gene in the myofibroblasts that makes a specific subset of proteins called alpha v integrins blocks the ability of these cells to trigger activation of TGF beta. Furthermore, they were able to replicate the effect of the gene deletion by treatment with a small molecule compound, thus opening the door to a potential new therapy for patients.

"This is the first foray into targeting not just a single integrin, but rather several integrins that appear to be working in concert to promote fibrosis," said David Griggs, Ph.D., Director of Biology at Saint Louis University's Center for World Health and Medicine and an author of the paper.

"We have developed small molecular compounds that selectively inhibit these integrins, which suppress TGF beta protein, and these have been effective in animal models of lung and liver fibrosis."

The small molecule was not only able to prevent fibrosis; it made fibrosis less severe even when the treatment was started after fibrosis had begun, Griggs added.

"It's really a platform technology that could be applied to a number of fibrotic conditions," Griggs said.

In tandem with the drug discovery research, scientists working on another part of the study found they could protect mice from pulmonary fibrosis, liver fibrosis and renal fibrosis by deleting a gene that makes the same specific integrins in myofibroblasts that were targeted by the drug.

"We want to hit the integrins that are linked to fibrosis, but leave integrins that are not involved in fibrosis alone," said Peter Ruminski, Executive Director of Saint Louis University's Center for World Health and Medicine and an author of the paper. "We're trying to bring TGF beta levels back to normal."

Fibrosis, which can occur in any of the body's organs, can contribute to deadly diseases by preventing organs from functioning properly because the fibrotic tissue hardens and swells. For instance, there is no FDA-approved treatment for pulmonary fibrosis, which has a high mortality rate and affects up to 150,000 Americans. Because there are no available drug treatments for pulmonary fibrosis in the US, the only effective therapy is an organ transplant. However transplants are expensive and demand for organs exceeds the supply, creating the need for more effective therapies.

The next steps, Ruminski said, are to determine exactly how much of the compound is needed to allow normal healing to occur instead of fibrosis. Scientists also need to study the best way to deliver the drug. Different fibrotic conditions could warrant different delivery methods, Ruminski speculated. For instance, an inhaled delivery method could be better to treat pulmonary fibrosis or a topical cream could be preferable for skin scarring, he said.


Story Source:

The above story is based on materials provided by Saint Louis University Medical Center. Note: Materials may be edited for content and length.


Journal Reference:

  1. Neil C Henderson, Thomas D Arnold, Yoshio Katamura, Marilyn M Giacomini, Juan D Rodriguez, Joseph H McCarty, Antonella Pellicoro, Elisabeth Raschperger, Christer Betsholtz, Peter G Ruminski, David W Griggs, Michael J Prinsen, Jacquelyn J Maher, John P Iredale, Adam Lacy-Hulbert, Ralf H Adams, Dean Sheppard. Targeting of αv integrin identifies a core molecular pathway that regulates fibrosis in several organs. Nature Medicine, 2013; DOI: 10.1038/nm.3282

Cite This Page:

Saint Louis University Medical Center. "Research offers way to disrupt fibrosis." ScienceDaily. ScienceDaily, 10 November 2013. <www.sciencedaily.com/releases/2013/11/131110184305.htm>.
Saint Louis University Medical Center. (2013, November 10). Research offers way to disrupt fibrosis. ScienceDaily. Retrieved September 23, 2014 from www.sciencedaily.com/releases/2013/11/131110184305.htm
Saint Louis University Medical Center. "Research offers way to disrupt fibrosis." ScienceDaily. www.sciencedaily.com/releases/2013/11/131110184305.htm (accessed September 23, 2014).

Share This



More Health & Medicine News

Tuesday, September 23, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Liberia Pleads for Help to Fight Ebola

Liberia Pleads for Help to Fight Ebola

AP (Sep. 22, 2014) Liberia's finance minister is urging the international community to quickly follow through on pledges of cash to battle Ebola. Bodies are piling up in the capital Monrovia as the nation awaits more help. (Sept. 22) Video provided by AP
Powered by NewsLook.com
Ebola Doctor Says Border Controls Critical

Ebola Doctor Says Border Controls Critical

AP (Sep. 22, 2014) A Florida doctor who helped fight the expanding Ebola outbreak in West Africa says the disease can be stopped, but only if nations quickly step up their response and make border control a priority. (Sept. 22) Video provided by AP
Powered by NewsLook.com
Global Ebola Aid Increasing But Critics Say It's Late

Global Ebola Aid Increasing But Critics Say It's Late

Newsy (Sep. 21, 2014) More than 100 tons of medical supplies were sent to West Africa on Saturday, but aid workers say the global response is still sluggish. Video provided by Newsy
Powered by NewsLook.com
Sierra Leone in Lockdown to Control Ebola

Sierra Leone in Lockdown to Control Ebola

AP (Sep. 21, 2014) Sierra Leone residents remained in lockdown on Saturday as part of a massive effort to confine millions of people to their homes in a bid to stem the biggest Ebola outbreak in history. (Sept. 20) Video provided by AP
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:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

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