The Scavenger Function of LSECs, a Regulator of Liver Diseases

Liver sinusoidal endothelial cells are highly specialized endothelial cells that contribute to liver homeostasis through their remarkable scavenger function. Through a broad repertoire of scavenger receptors, including mannose receptor, scavenger receptor H, fragment crystallizable gamma receptor IIb, LSECs efficiently clear waste and toxins, altering drug distribution and metabolism. However, this scavenger function can be disrupted by aging, toxins, and transcription factors, thereby promoting the accumulation of harmful substances within the hepatic microenvironment. Impaired LSEC scavenger function contributes to the initiation and progression of multiple liver diseases, such as metabolic dysfunction associated steatotic liver disease, alcoholic liver disease, liver fibrosis, hepatocellular carcinoma, and antibody-based drug-related liver injury. Emerging pharmacological evidence suggests that antioxidant agents, anti-angiogenic strategies and anti-inflammatory interventions may partially restore the expression or function of LSEC scavenger receptors to alleviate liver diseases. In summary, the scavenger function of LSECs serves as a key gatekeeper in liver homeostasis, and targeted modulation of this function holds great potential for the treatment of liver diseases.