IL32 downregulation lowers triglycerides and type I collagen in di-lineage human primary liver organoids

• DOI: 10.1016/j.xcrm.2023.101352
• Publication Date: 2024-01-16T15:36:53Z
• Authors: Kavitha Sasidharan; Andrea Caddeo; Oveis Jamialahmadi; Francesca Rita Noto; Melissa Tomasi; Francesco Malvestiti; Ester Ciociola; Federica Tavaglione; Rosellina M. Mancina; Alessandro Cherubini; Cristiana Bianco; Angela Mirarchi; Ville Männistö; Jussi Pihlajamäki; Vesa Kärjä; Stefania Grimaudo; Panu K. Luukkonen; Sami Qadri; Hannele Yki-Järvinen; Salvatore Petta; Silvia Manfrini; Umberto Vespasian...; Vincenzo Bruni; Luca Valenti; Stefano Romeo
• Keywords: Organoid; Hepatic stellate cell; Pathogenesis

Steatotic liver disease (SLD) prevails as the most common chronic yet lack approved treatments due to incomplete understanding of pathogenesis. Recently, elevated hepatic and circulating interleukin 32 (IL-32) levels were found in individuals with severe SLD. However, mechanistic link between IL-32 intracellular triglyceride metabolism remains be elucidated. We demonstrate vitro that incubation IL-32β protein leads an increase synthesis, while downregulation IL32 by small interfering RNA lower synthesis secretion organoids from human primary hepatocytes. This reduction requires upregulation Phospholipase A2 group IIA (PLA2G2A). Furthermore, results type I collagen di-lineage organoids. Finally, we identify a genetic variant (rs76580947) associated protection against SLD measured non-invasive tests. These data suggest may beneficial