New Intercellular Communication Mechanism Found in Liver Fibrosis Progression

A recent study led by Dr. Takao Seki, Assistant Professor, and Dr. Hiroyasu Nakano, Specially Appointed Professor, at the Faculty of Medicine, Toho University, has unveiled an intricate intercellular network that plays a pivotal role in the progression of liver fibrosis. Published in the international journal *iScience* in June 2026, the research highlights the critical involvement of hepatic stellate cells and two key molecules: fibroblast growth factor 18 (FGF18) and osteopontin (OPN) in this pathological condition.

Liver fibrosis, characterized by the stiffening and scarring of the liver, typically arises from chronic liver diseases, including chronic hepatitis and metabolic dysfunction-associated steatohepatitis (MASH). As advanced fibrosis can lead to severe health complications such as cirrhosis and liver cancer, understanding its underlying mechanisms is essential for developing effective therapeutic interventions.

According to the findings of the study, under normal circumstances, hepatic stellate cells are dormant and primarily function to store vitamin A. However, liver injury prompts their transformation into myofibroblasts, which actively produce collagen and other components of the extracellular matrix, thus contributing to fibrosis. The researchers discovered that activated hepatic stellate cells, when stimulated with FGF18, significantly increase the production of OPN. This increase, in turn, activates neighboring quiescent stellate cells, creating a self-perpetuating cycle of fibrosis progression.

Dr. Yuichi Tsuchiya, Associate Professor at the Faculty of Pharmaceutical Sciences, Toho University, who collaborated on the research, explains, "The study identifies a novel mechanism of intercellular communication among hepatic stellate cells, revealing how fibrosis can propagate through direct cell-to-cell signaling. This is a crucial insight into the dynamic nature of liver fibrosis development."

The study employed a mouse model of liver fibrosis to further validate its findings. Researchers observed that OPN transmits signals via a cell surface receptor known as integrin, underscoring the complexity of the molecular interactions at play. The discovery that OPN specifically targets quiescent stellate cells, rather than already activated ones, suggests a sophisticated feedback loop that amplifies fibrotic activity across the liver tissue.

The implications of these findings extend into therapeutic realms as well. The FGF18-OPN axis presents a promising target for future treatments. Given that FGF18 selectively acts on hepatic stellate cells, therapies based on this specific pathway may provide targeted interventions that minimize the broader adverse effects associated with conventional liver-targeted drugs. Dr. Minoru Tanaka, Division Chief at the National Center for Global Health and Medicine Research Institute, noted, "The potential to develop cell-specific therapies from this research could revolutionize how we approach treatment for liver fibrosis."

In light of the growing incidence of liver diseases globally, this research is timely. Reports from the World Health Organization indicate that liver disease is becoming one of the leading causes of mortality worldwide, underscoring the urgency of developing effective treatment modalities. A 2023 report from the American Liver Foundation highlighted that liver disease cases have increased by over 30% in the last decade, necessitating immediate attention and action from the medical community.

The intricate interplay between cellular mechanisms in liver fibrosis emphasizes the need for continued research in this area. As scientists unravel the complexities of liver disease, there is hope that targeted therapies will emerge, offering new avenues for patient care and improved outcomes. The findings from Toho University represent a significant contribution to this ongoing effort, potentially paving the way for innovative strategies in the battle against liver fibrosis.