Navigation Links
Research by Saint Louis University scientists offers way to disrupt fibrosis
Date:11/10/2013

ST. LOUIS 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 Nov. 10 in the advance online 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.


'/>"/>

Contact: Nancy Solomon
solomonn@slu.edu
314-977-8017
Saint Louis University
Source:Eurekalert

Related biology news :

1. Research reveals roles for exercise and diet in aging, depression
2. NSF awards to UT Arlington researchers will fuel sustainable solutions
3. OHSU Vollum Institute research gives new insight into how antidepressants work in the brain
4. Researchers uncover origins of cattle farming in China
5. UT Southwestern researchers identify how body clock affects inflammation
6. Researchers suggest plan to address hypoxia in Gulf of Mexico
7. Researchers advocate for climate adaptation science
8. UMMS researchers answer century old question about 3D structure of mitotic chromosomes
9. NIH funds researchers using light to control and monitor neural activity
10. Researchers regrow hair, cartilage, bone, soft tissues
11. Research shows that the more chocolate you eat, the lower your body fat level is
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/23/2017)... and ITHACA, N.Y. , ... and Cornell University, a leader in dairy research, today ... bioinformatics designed to help reduce the chances that the ... the onset of this dairy project, Cornell University has ... for Sequencing the Food Supply Chain, a food safety ...
(Date:5/16/2017)... May 16, 2017  Veratad Technologies, LLC ( www.veratad.com ... age and identity verification solutions, announced today they will ... 2017, May 15 thru May 17, 2017, in ... International Trade Center. Identity impacts the ... in today,s quickly evolving digital world, defining identity is ...
(Date:4/24/2017)... 24, 2017 Janice Kephart , ... Identity Strategy Partners, LLP (IdSP) , today issues ... President Trump,s March 6, 2017 Executive Order: ... vetting can be instilled with greater confidence, enabling ... all refugee applications are suspended by until at ...
Breaking Biology News(10 mins):
(Date:8/16/2017)... and OXFORD, England , Aug. 16, ... consortium for biotech executive search and leadership development, and Virdis ... sectors, have created an exclusive alliance that enables clients to ... "For our clients here in the ... unparalleled access to a diverse population of leadership talent throughout ...
(Date:8/15/2017)... ... August 15, 2017 , ... ... largest Asian exhibitions for analytical and scientific instruments. This year’s symposium, organized by ... Approaches in Mass Spectrometry for Bioanalytical Applications.” This dynamic presentation will discuss novel ...
(Date:8/15/2017)... ... August 15, 2017 , ... Coffea arabica ... biotic and abiotic factors. During this educational webinar, participants will learn about the ... as gain a better understanding of how genomics is important for coffee breeding ...
(Date:8/14/2017)... ... August 14, 2017 , ... The Conference Forum ... which will take place on September 6, 2017 at the Marriott Copley Place in ... of Experimental Medicine, Informatics, and Regulatory Strategy, Pfizer Innovative Research Lab, Pfizer, who leads ...
Breaking Biology Technology: