Butyrylcholinesterase alleviates hepatic stellate cell activation via paracrine muscarinic signalling.

Hepatocyte-derived butyrylcholinesterase reduces liver fibrosis by regulating acetylcholine levels and muscarinic receptor signaling, with deficiency increasing fibrosis severity.

• Why it matters: Understanding the mechanisms behind liver fibrosis is crucial for developing targeted therapies, as current treatments are limited and fibrosis progression leads to cirrhosis and liver failure.
• What they did: The study measured BuChE expression in patient biopsies and mouse models, using genetic, pharmacological, and molecular approaches to assess its role in fibrosis and cholinergic signaling pathways.
• The result: Loss of BuChE activity causes ACh accumulation, activating hepatic stellate cells via ChRM3-NF-κB signaling, and modulating this pathway could offer new therapeutic strategies to prevent or treat liver fibrosis.