Signaling Pathway Sheds Light on Chronic Liver Disease Therapy

Digestive hormone found to reduce liver fibrosis associated with cholestasis.

High levels of secretin may play a key role in the management of select chronic liver diseases.

A study published in Hepatology found that in animal models, the digestive hormone secretin reduced liver fibrosis associated with cholestasis. Additionally, the antagonist was also able to turn off related genes, even in those genetically predisposed to fibrosis.

“One of the things we also show in this paper is that the secretin/secretin receptor pathway is activated in human tissue samples of patients with cholestatic liver disease, as compared to healthy people,” said senior study author Gianfranco Alpini, PhD. “The next step would be more translational studies to look at additional types of cholestatic liver disease in humans.”

Previous work conducted by Alpini and his team found that secretin can cause cholangiocytes to proliferate, blocking bile secretion. A majority of the time, too much proliferation is the cause of the problem; however, some individuals experience a loss of bile ducts.

This type of condition can cause similar digestive problems to fibrosis, because both conditions cause bile to collect in the liver instead of going where needed. Theoretically, a solution to this problem could be to use secretin to stimulate biliary growth.

“This work might help manage hepatobiliary disorders with extrahepatic bile duct obstruction and primary sclerosing cholangitis,” said study author Fanyin Meng, MD, PhD.

Further studies on the effects of secretin in other parts of the body, such as the heart or brain, may also provide insight into how the neuroendocrine hormone works outside of the gastrointestinal tract.

“It is very exciting that we were able to identify the specific signaling pathway in cholangiocytes that we might be able to target therapeutically in this cholestatic disease,” said study author Shannon Glaser, PhD. “I think if you caught it early enough, you might be able to target this pathway to alleviate the beginnings of fibrosis, and that will prevent some of the other cells being damaged and the problem cascading into liver failure.”