Central role of Prominin-1 in lipid rafts during liver regeneration
Central role of Prominin-1 in lipid rafts during liver regeneration
Abstract Prominin-1 (PROM1), 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 investigated the role of PROM1 in lipid rafts with a precise molecular mechanism during liver regeneration. We found that the expression of PROM1 increased during liver regeneration after 2/3 partial hepatectomy (PHx) or CCl4 injection. Interestingly, hepatocyte proliferation and liver regeneration were attenuated in liver-specific Prom1 knockout (Prom1LKO) mice compared to wild-type (Prom1f/f) mice. Detailed mechanistic studies revealed that PROM1 interacted with the interleukin-6 signal transducer glycoprotein 130 (GP130) and confined GP130 to lipid rafts so that STAT3 signaling by IL-6 was effectively activated. Moreover, the overexpression of the glycosylphosphatidylinsositol (GPI)-anchored first extracellular domain of PROM1 (PROM1GPI-EX1), which is a domain that binds to GP130, rescued the proliferation of hepatocytes and liver regeneration in Prom1LKO mice. PROM1 is upregulated in hepatocytes during liver regeneration, and upregulated PROM1 recruits GP130 into lipid rafts and activates the IL6-GP130-STAT3 axis. Thus, we conclude that PROM1 plays an important role in lipid rafts during liver regeneration and might be a promising target for therapeutic applications of liver transplantation.
Lee Ji-Won、Ko Young-Gyu、Kim Jun Seok、Lee Jae-Seon、Yu Dong-Min、Kim Arum、Koo Seung-Hoi、Hong Jeong-Ho、Jo Sung-Je、Lee Hyun、Lee Myoungwoo、Bahn Myeong-Suk
Tunneling Nanotube Research Center, Korea University||Division of Life Sciences, Korea UniversityTunneling Nanotube Research Center, Korea University||Division of Life Sciences, Korea UniversityTunneling Nanotube Research Center, Korea University||Division of Life Sciences, Korea UniversityDepartment of Molecular Medicine, College of Medicine, Inha UniversityTunneling Nanotube Research Center, Korea University||Division of Life Sciences, Korea UniversityTunneling Nanotube Research Center, Korea University||Division of Life Sciences, Korea UniversityTunneling Nanotube Research Center, Korea University||Division of Life Sciences, Korea UniversityTunneling Nanotube Research Center, Korea University||Division of Life Sciences, Korea UniversityTunneling Nanotube Research Center, Korea University||Division of Life Sciences, Korea UniversityTunneling Nanotube Research Center, Korea University||Division of Life Sciences, Korea UniversityTunneling Nanotube Research Center, Korea University||Division of Life Sciences, Korea UniversityTunneling Nanotube Research Center, Korea University||Division of Life Sciences, Korea University
基础医学分子生物学生理学
Lee Ji-Won,Ko Young-Gyu,Kim Jun Seok,Lee Jae-Seon,Yu Dong-Min,Kim Arum,Koo Seung-Hoi,Hong Jeong-Ho,Jo Sung-Je,Lee Hyun,Lee Myoungwoo,Bahn Myeong-Suk.Central role of Prominin-1 in lipid rafts during liver regeneration[EB/OL].(2025-03-28)[2025-05-21].https://www.biorxiv.org/content/10.1101/2022.01.20.477032.点此复制
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