| Literature DB >> 36266314 |
Myeong-Suk Bahn1, Dong-Min Yu1, Myoungwoo Lee1, Sung-Je Jo1, Ji-Won Lee1, Ho-Chul Kim1, Hyun Lee1, Hong Lim Kim2, Arum Kim1, Jeong-Ho Hong1, Jun Seok Kim1, Seung-Hoi Koo1, Jae-Seon Lee3, Young-Gyu Ko4.
Abstract
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 CCl4 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.Entities:
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Year: 2022 PMID： 36266314 PMCID： PMC9585078 DOI： 10.1038/s41467-022-33969-4
Source DB: PubMed Journal: Nat Commun ISSN： 2041-1723 Impact factor: 17.694