Attenuating chemical signals in fibrotic process may reduce scarring in humans

July 1, 2012

New research has identified the signaling pathway through which mechanical forces play a major role in the fibrotic process of wound healing and scarring. Modulating this pathway in mice significantly reduced scarring and may offer a therapeutic target to reduce scarring in humans, says Geoffrey C. Gurtner, M.D.

Key Points

National report - New research has identified the signaling pathway through which mechanical forces play a major role in the fibrotic process of wound healing and scarring. Modulating this pathway in mice significantly reduced scarring and may offer a therapeutic target to reduce scarring in humans, says Geoffrey C. Gurtner, M.D.

"Unlike a piece of leather, your skin responds to mechanical forces in a very active way that upregulates inflammation and leads to all of the bad things that we see with both inflammation and fibrosis," he adds.

Dr. Gurtner found he could significantly reduce scarring in wild type mice by applying a small molecule compound that blocks FAK. The gross scar area was 170 percent less compared to controls, and scar matrix density was reduced - epithelial thickness (35 percent), epithelial proliferation (57 percent), and dermal proliferation (28 percent). The work was published in Nature Medicine in December 2011.

"Inflammation is a necessary part of the response to injury. You need it to bring in cells, the monocytes and the macrophages that are going to release the growth factors that are going to lead to collagen deposition and new blood vessel growth," he says. "But each time you have any level of mechanical stimulation you stimulate focal adhesion kinase; that stimulates monocyte and macrophage recruitment to the wound - it creates this vicious cycle.

"The challenge is trying to figure out what are the places where you can try to reduce these processes, versus what are the parts that are non-negotiable," Dr. Gurtner says. "If you can minimize the duration (of that inflammatory burst) without totally obliterating it, I think that is probably the preferred pathway to allow tissue to heal and come as close to regeneration as it possibly can."