A team of investigators led by Dr. James Luyendyk at the MSU College of Veterinary Medicine has uncovered a new pathway that stimulates liver repair. Using an experimental setting of acetaminophen overdose, Luyendyk’s team found that liver injury activated blood clotting, which stimulated liver repair.

“This discovery could lead to new strategies to promote liver regeneration.” “This pathway of liver repair has never before been described,” Luyendyk said.

“Tissue injury is tightly connected to activation of blood clotting, meaning this new pathway could be very important for liver damage driven by numerous causes,” Luyendyk said. His laboratory is currently defining the role of this particular pathway in liver cirrhosis, liver autoimmunity, and obesity.

Acetaminophen, a widely used pain reliever and fever reducer, is the active ingredient in more than 600 over-the-counter and prescription medications. Acetaminophen overdose is a leading cause of drug-induced liver failure in the United States.

The liver is often capable of responding to liver damage by triggering a repair response that can restore normal liver function. However, if this process is insufficient or fails, liver damage persists, leading to acute liver failure, a condition associated with faulty liver function and often necessitating liver transplantation.

“We were very surprised because normally the blood clotting process is assumed to be pathologic,” Luyendyk said.

Fibrinogen is a large, complex, soluble blood plasma protein. During coagulation, it is converted to insoluble fibrin deposits, a component of blood clots. Luyendyk and his team discovered that fibrin deposits are critical to liver repair after acetaminophen overdose.

The fibrin molecule plays a key role in activating macrophages, a type of immune cell that helps remove cellular debris. In their published study, Luyendyk and his colleague Dr. Anna Kopec report that this specific activity of fibrin is required to drive repair of the injured liver. Kopec notes that “this activity of fibrinogen can in principle be enhanced by drugs, potentially without affecting the blood clotting process itself.”

Current treatments for acetaminophen poisoning are focused on reducing acetaminophen toxicity. But in many cases, patients already have injury when they arrive at the hospital, at which point the window for treatment with existing therapies may have passed.

“Discovery of drugs that can promote repair of the already injured liver would address an unmet need,” Luyendyk said.

Both investigators are optimistic that their continued research will encourage translation of this concept and ultimately improve strategies to improve liver repair in patients.

Read the original manuscript here.

Patty Bonito

Office of Communications

College of Veterinary Medicine

Michigan State University

James P. Luyendyk, PhD

luyendyk@msu.edu

Phone: 517-884-2057

Pathobiology and Diagnostic Investigation Michigan State University