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New Insights into Liver Fibrosis: Cell Communication Discovery
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By Amelia sanchez | TOKYO – 2025/06/21 21:27:45
A new study has revealed a previously unknown communication network between liver cells that contributes to liver fibrosis, offering potential new therapeutic targets.
Liver fibrosis, characterized by the stiffening and scarring of the liver, is a common consequence of chronic liver diseases, including chronic hepatitis and metabolic dysfunction-associated steatohepatitis (MASH). Because advanced fibrosis can progress to cirrhosis or liver cancer, understanding its mechanisms is crucial for developing effective treatments.
A research team led by Dr. Takao Seki and dr. Hiroyasu Nakano at the Faculty of Medicine,Toho University,has identified a novel intercellular network that promotes liver fibrosis. Their findings emphasize the significant roles of hepatic stellate cells and two key molecules: the growth factor FGF18 and osteopontin (OPN), a pro-fibrotic mediator.
Under normal conditions, hepatic stellate cells remain inactive and store vitamin A. However, when the liver is injured, they transform into myofibroblasts, which actively produce collagen and other extracellular matrix components, contributing to fibrosis. This study demonstrates how these stellate cells interact to propagate fibrotic activity.
The researchers initially showed that stimulating activated hepatic stellate cells with FGF18 substantially increases OPN production. They further demonstrated that OPN acts on neighboring quiescent stellate cells, inducing their activation and creating a positive feedback loop. Notably, OPN specifically targets quiescent cells, effectively spreading fibrosis in a step-by-step manner. Using a mouse model of liver fibrosis, the team discovered that OPN transmits signals via integrin, a cell surface receptor, highlighting how molecular communication among stellate cells drives the fibrotic process.
Implications of the Findings
“fibrosis is shown to be a dynamic and coordinated response involving cell-cell signaling and environmental cues.”
These findings identify a novel self-amplifying intercellular communication system in liver fibrosis, mediated by FGF18 and OPN. Rather than being a consequence of a single molecule, “fibrosis is shown to be a dynamic and coordinated response involving cell-cell signaling and environmental cues.” This discovery offers a new outlook on the pathogenesis of liver fibrosis.
The FGF18-OPN axis also presents a promising therapeutic target.As FGF18 selectively acts on hepatic stellate cells, therapies based on this pathway may offer cell-specific interventions that avoid the broad effects of conventional liver-targeted drugs.
This research, conducted in collaboration with Dr. Yuichi Tsuchiya and Dr. Minoru Tanaka, was published in the international journal iScience in June 2026.
