Discovery of a Cellular Network Accelerating Liver Fibrosis

Recent research by scientists at Toho University has uncovered a novel intercellular communication system that plays a significant role in the progression of liver fibrosis, a condition characterized by scarring and stiffening of the liver tissue. Liver fibrosis commonly results from chronic liver diseases such as hepatitis and metabolic-associated steatohepatitis (MASH). If left untreated, advanced fibrosis can lead to severe complications including cirrhosis and liver cancer, emphasizing the importance of understanding its underlying mechanisms.

Led by Dr. Takao Seki and Dr. Hiroyasu Nakano, the study published in iScience reveals how hepatic stellate cells, which normally store vitamin A, transform into myofibroblasts during liver injury. These activated stellate cells are responsible for producing collagen and other extracellular matrix components that contribute to fibrosis. The researchers identified that the growth factor FGF18 stimulates these stellate cells to produce osteopontin (OPN), a molecule that further amplifies fibrotic activity.

The study demonstrates that OPN influences neighboring quiescent stellate cells, inducing their activation and creating a feedback loop that propagates fibrosis. Notably, OPN targets only the dormant stellate cells and not those already activated, which suggests a mechanism for the stepwise spread of fibrosis within the liver. Using mouse models, the team found that OPN signals through a receptor called integrin, promoting intercellular communication that accelerates scarring.

This discovery points to a complex, dynamic system driven by specific cell signals, challenging the traditional view of fibrosis as a simple consequence of certain molecules. It highlights the potential of targeting the FGF18–OPN pathway for therapeutic intervention. Since FGF18 acts specifically on hepatic stellate cells, drugs designed to disrupt this axis could provide precise treatment options with fewer side effects compared to conventional therapies.

Overall, this research advances our understanding of liver fibrosis's cellular processes and opens new avenues for developing targeted therapies to combat chronic liver diseases. The collaborative effort involved contributions from other experts, including Dr. Yuichi Tsuchiya and Dr. Minoru Tanaka, further emphasizing the significance of these findings for future clinical applications.

Source: https://medicalxpress.com/news/2025-06-cellular-communication-network-liver-fibrosis.html