| Title: | IL32 downregulation lowers triglycerides and type I collagen in di-lineage human primary liver organoids |
| Journal: | Cell Reports Medicine |
| Published: | 16 Jan 2024 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/38232700/ |
| DOI: | https://doi.org/10.1016/j.xcrm.2023.101352 |
| URL: | http://www.cell.com/article/S2666379123005694/pdf |
Publication 8938
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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-32β 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.</p>
25 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 Vespasiani-Gentilucci
- Vincenzo Bruni
- Luca Valenti
- Stefano Romeo
1 Application
| Application ID | Title |
|---|---|
| 37142 | UNDERSTANDING THE GENETIC ARCHITECTURE OF CHRONIC LIVER DISEASE |
Enabling scientific discoveries that improve human health