Nature communications, 2022-10, Vol.13 (1), p.6219-6219, Article 6219
2022
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- Autor(en) / Beteiligte
- Titel
- Central role of Prominin-1 in lipid rafts during liver regeneration
- Ist Teil von
- Nature communications, 2022-10, Vol.13 (1), p.6219-6219, Article 6219
- Ort / Verlag
- London: Nature Publishing Group UK
- Erscheinungsjahr
- 2022
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Prominin-1, a lipid raft protein, is required for maintaining cancer stem cell properties in hepatocarcinoma cell lines, but its physiological roles in the liver have not been well studied. Here, we investigate the role of Prominin-1 in lipid rafts during liver regeneration and show that expression of Prominin-1 increases after 2/3 partial hepatectomy or CCl 4 injection. Hepatocyte proliferation and liver regeneration are attenuated in liver-specific Prominin-1 knockout mice compared to wild-type mice. Detailed mechanistic studies reveal that Prominin-1 interacts with the interleukin-6 signal transducer glycoprotein 130, confining it to lipid rafts so that STAT3 signaling by IL-6 is effectively activated. The overexpression of the glycosylphosphatidylinsositol-anchored first extracellular domain of Prominin-1, which is the domain that binds to GP130, rescued the proliferation of hepatocytes and liver regeneration in liver-specific Prominin-1 knockout mice. In summary, Prominin-1 is upregulated in hepatocytes during liver regeneration where it recruits GP130 into lipid rafts and activates the IL6-GP130-STAT3 axis, suggesting that Prominin-1 might be a promising target for therapeutic applications in liver transplantation. Bahn et al explore the role of the lipid raft protein Prominin-1 in liver regeneration. They show that Prominin-1 promotes hepatocyte proliferation after acute liver injury by interacting with the signal transducer GP130, confining it to lipid rafts and activating IL-6 signaling pathway and eventual activation of STAT3.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2041-1723eISSN: 2041-1723DOI: 10.1038/s41467-022-33969-4Titel-ID: cdi_doaj_primary_oai_doaj_org_article_44a2b730a3d24d5aa6b5b8449e0f3f16
- Format
- –
- Schlagworte
- 13/1, 13/109, 13/21, 13/95, 14/19, 14/34, 38/70, 38/88, 631/443, 631/80/641/1655, 631/80/86, 64/60, 82/29, 82/51, 82/80, AC133 Antigen - genetics, Animals, Carbon tetrachloride, Confining, Cytokine Receptor gp130 - genetics, Cytokine Receptor gp130 - metabolism, Domains, Glycoprotein gp130, Glycoproteins, Hepatectomy, Hepatocytes, Humanities and Social Sciences, Interleukin 6, Interleukin-6 - metabolism, Lipid rafts, Lipids, Liver, Liver Regeneration - physiology, Liver transplantation, Membrane Microdomains - metabolism, Mice, Mice, Knockout, multidisciplinary, Proteins, Rafts, Regeneration, Rodents, Science, Science (multidisciplinary), Signal transduction, Signaling, Stat3 protein, Stem cells, Therapeutic applications, Transplantation