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  • Sasidharan, KavithaGothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine (author)

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

  • Article/chapterEnglish2024

Publisher, publication year, extent ...

  • 2024

Numbers

  • LIBRIS-ID:oai:gup.ub.gu.se/334308
  • https://gup.ub.gu.se/publication/334308URI
  • https://doi.org/10.1016/j.xcrm.2023.101352DOI

Supplementary language notes

  • Language:English

Part of subdatabase

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • 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 invitro 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.

Subject headings and genre

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  • Caddeo, AndreaGothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine(Swepub:gu)xcadda (author)
  • Oveis, JamialahmadiGothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine (author)
  • Noto, Francesca R,1995Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine(Swepub:gu)xritfr (author)
  • Tomasi, Melissa (author)
  • Malvestiti, Francesco (author)
  • Ciociola, EsterGothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine(Swepub:gu)xcioce (author)
  • Tavaglione, FedericaGothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine(Swepub:gu)xtavfe (author)
  • Mancina, Rosellina MargheritaGothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine(Swepub:gu)xmanro (author)
  • Cherubini, Alessandro (author)
  • Bianco, Cristiana (author)
  • Mirarchi, Angela (author)
  • Männistö, Ville (author)
  • Pihlajamäki, Jussi (author)
  • Kärjä, Vesa (author)
  • Grimaudo, Stefania (author)
  • Luukkonen, Panu K (author)
  • Qadri, Sami (author)
  • Yki-Järvinen, Hannele (author)
  • Petta, Salvatore (author)
  • Manfrini, Silvia (author)
  • Vespasiani-Gentilucci, Umberto (author)
  • Bruni, Vincenzo (author)
  • Valenti, Luca (author)
  • Romeo, Stefano,1976Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine(Swepub:gu)xroste (author)
  • Göteborgs universitetInstitutionen för medicin, avdelningen för molekylär och klinisk medicin (creator_code:org_t)

Related titles

  • In:Cell reports. Medicine5:12666-3791

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