By targeting a pathway that turns off the trigger for the major molecular mediator of fibrosis, a protein called Transforming Growth Factor (TGF) beta, researchers believe they have discovered a new way to intervene in the molecular and cellular cascade that causes fibrosis, according to findings published online ahead of print in the journal Nature Medicine.

“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, PhD, 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.”

TGF beta, which is normally present in the body in an inactive state, stimulates cells called myofibroblasts to produce excess collagen, which is a principle component of scars. A gene in the myofibroblasts makes a specific subset of proteins called alpha v integrins. By removing that gene, blocks the ability of these cells to trigger activation of TGF beta.

The team was also 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. 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, according to Griggs who believes it is a “platform technology that could be applied to a number of fibrotic conditions.”