biostudies-literatureMederacke INCATS NIH HHSNIDDK NIH HHSNCI NIH HHSWellcome Trusteabe5795https://www.ebi.ac.uk/biostudies/studies/S-EPMC9436006biostudies-literatureUnknown14(639)Fibrosis contributes to ~45% of deaths in western countries. In chronic liver disease, fibrosis is a major factor determining outcomes, but efficient antifibrotic therapies are lacking. Although platelet-derived growth factor and transforming growth factor-β constitute key fibrogenic mediators, they do not account for the well-established link between cell death and fibrosis in the liver. Here, we hypothesized that damage-associated molecular patterns (DAMPs) may link epithelial cell death to fibrogenesis in the injured liver. DAMP receptor screening identified purinergic receptor P2Y14 among several candidates as highly enriched in hepatic stellate cells (HSCs), the main fibrogenic cell type of the liver. Conversely, P2Y14 ligands uridine 5'-diphosphate (UDP)-glucose and UDP-galactose werScience translational medicineThe purinergic P2Y14 receptor links hepatocyte death to hepatic stellate cell activation and fibrogenesis in the liver.PMC9436006219542/Z/19/ZR01 DK116620UL1 TR001873R01 DK124104104366/Z/14/ZR01 CA200597P30 CA013696Vondran FWRAnke HHenderson NCSancho-Bru PHamberger FRavichandra ASmith JRHuebener PBaehre HSchwabe RFTabas ISun QBrundu FMederacke IAffo SChen YRothlin CVMartinez Garcia de la Torre RAFilliol AShi HNair AHernandez CfalseThe purinergic P2Y14 receptor links hepatocyte death to hepatic stellate cell activation and fibrogenesis in the liver.Fibrosis contributes to ~45% of deaths in western countries. In chronic liver disease, fibrosis is a major factor determining outcomes, but efficient antifibrotic therapies are lacking. Although platelet-derived growth factor and transforming growth factor-β constitute key fibrogenic mediators, they do not account for the well-established link between cell death and fibrosis in the liver. Here, we hypothesized that damage-associated molecular patterns (DAMPs) may link epithelial cell death to fibrogenesis in the injured liver. DAMP receptor screening identified purinergic receptor P2Y14 among several candidates as highly enriched in hepatic stellate cells (HSCs), the main fibrogenic cell type of the liver. Conversely, P2Y14 ligands uridine 5'-diphosphate (UDP)-glucose and UDP-galactose wer2022-01-01T00:00:00Z2022 Apr2025-04-26T15:34:40.495Z2025-04-06T14:56:59.382ZS-EPMC94360063538533910.1126/scitranslmed.abe5795