Findings have implications for heart failure, muscular dystrophy and pulmonary disorders

Researchers at Cincinnati Children’s have discovered a previously unknown function for a protein that could lead to new drugs for battling inflammation and tissue fibrosis.

The study finds that heart attacks and other types of injury activate a tissue repair pathway controlled by the protein TRPC6. The protein prompts cells called fibroblasts to change into myofibroblasts, which in turn secrete extracellular matrix, an important substance needed for tissue remodeling. Over-activating this pathway can lead to excessive inflammation and scarring.

The study, led by Jeffery Molkentin, PhD, and Jennifer Davis, PhD, of the Heart Institute at Cincinnati Children’s, was published Sept. 27, 2012 in Developmental Cell.

“Our study suggests that a TRPC inhibitor could be a good anti-fibrotic or anti-inflammatory agent in heart failure, muscular dystrophy, pulmonary disorders and other diseases where tissue fibrosis becomes a problem,” Molkentin says. “Meanwhile, activation of the TRPC pathway with an agonist compound could be used in select situations to enhance wound healing.”

Prior to the new findings, TRPC6 had not been associated with fibrosis, although it has been linked to other cellular functions in skin cells, kidneys and the brain.

Some TRPC inhibitors already are in early-stage development, although their initial design has not targeted heart disease, inflammation or fibrosis. The new study may expand the development focus, Molkentin says.