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

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