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

Sasidharan, K., Caddeo, A., Jamialahmadi, O., Noto, F.R., Tomasi, M., Malvestiti, F., et al. (2024). IL32 downregulation lowers triglycerides and type I collagen in di-lineage human primary liver organoids. CELL REPORTS MEDICINE, 5(1), 1-12 [10.1016/j.xcrm.2023.101352].

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

Grimaudo, Stefania;Petta, Salvatore;
2024-01-16

Abstract

Steatotic liver disease (SLD) prevails as the most common chronic liver disease 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, the mechanistic link between IL -32 and intracellular triglyceride metabolism remains to be elucidated. We demonstrate in vitro that incubation with IL -32b protein leads to an increase in intracellular triglyceride synthesis, while downregulation of IL32 by small interfering RNA leads to lower triglyceride synthesis and secretion in organoids from human primary hepatocytes. This reduction requires the upregulation of Phospholipase A2 group IIA (PLA2G2A). Furthermore, downregulation of IL32 results in lower intracellular type I collagen levels in di -lineage human primary hepatic organoids. Finally, we identify a genetic variant of IL32 (rs76580947) associated with lower circulating IL -32 and protection against SLD measured by non-invasive tests. These data suggest that IL32 downregulation may be beneficial against SLD.
16-gen-2024
Settore BIO/13 - Biologia Applicata
Settore MED/12 - Gastroenterologia
Sasidharan, K., Caddeo, A., Jamialahmadi, O., Noto, F.R., Tomasi, M., Malvestiti, F., et al. (2024). IL32 downregulation lowers triglycerides and type I collagen in di-lineage human primary liver organoids. CELL REPORTS MEDICINE, 5(1), 1-12 [10.1016/j.xcrm.2023.101352].
File in questo prodotto:
File Dimensione Formato  
IL 32 .pdf

accesso aperto

Tipologia: Versione Editoriale
Dimensione 4.86 MB
Formato Adobe PDF
4.86 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10447/636154
Citazioni
  • ???jsp.display-item.citation.pmc??? 0
  • Scopus 1
  • ???jsp.display-item.citation.isi??? 0
social impact