Cell Discovery | DR. Jing Yang：Estrogen receptor 1 signaling in hepatic stellate cells designates resistance to liver fibrosis

Abstract

we have elucidated a critical aspect of ESR1 signaling in HSCs designating resistance to liver fibrosis. Future research will help delineate the detailed mechanism underlying the ESR1-mediated transcriptional suppression of fibrosis-related genes, which may act via interactions with other transcriptional factors. It was recently reported that ESR1 could control the expression of the patatin-like phospholipase domain-containing 3 (PNPLA3) I148M variant in human hepatocytes, thus influencing the women’s susceptibility to MASLD. Moreover, previous research has suggested the involvement of mechanotransduction in liver fibrosis. Whether ESR1 signaling may influence the fibrogenic response of HSCs to such mechanical cues warrants more examination. Our in-depth understanding of the sexual dimorphism of liver fibrosis and its pathophysiological mechanisms will lead to better stratification of patients for diagnostic and therapeutic benefits.

Original Link：https://doi.org/10.1038/s41421-025-00783-3