Central role of Prominin-1 in lipid rafts during liver regeneration

Myeong Suk Bahn; Dong Min Yu; Myoungwoo Lee; Sung Je Jo; Ji Won Lee; Ho Chul Kim; Hyun Lee; Hong Lim Kim; Arum Kim; Jeong Ho Hong; Jun Seok Kim; Seung Hoi Koo; Jae Seon Lee; Young Gyu Ko

doi:10.1038/s41467-022-33969-4

Central role of Prominin-1 in lipid rafts during liver regeneration

Myeong Suk Bahn, Dong Min Yu, Myoungwoo Lee, Sung Je Jo, Ji Won Lee, Ho Chul Kim, Hyun Lee, Hong Lim Kim, Arum Kim, Jeong Ho Hong, Jun Seok Kim, Seung Hoi Koo, Jae Seon Lee, Young Gyu Ko

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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.

Original language	English
Article number	6219
Journal	Nature communications
Volume	13
Issue number	1
DOIs	https://doi.org/10.1038/s41467-022-33969-4
Publication status	Published - 2022 Dec

ASJC Scopus subject areas

Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)
General
Physics and Astronomy(all)

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s41467-022-33969-4

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title = "Central role of Prominin-1 in lipid rafts during liver regeneration",

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.",

author = "Bahn, {Myeong Suk} and Yu, {Dong Min} and Myoungwoo Lee and Jo, {Sung Je} and Lee, {Ji Won} and Kim, {Ho Chul} and Hyun Lee and Kim, {Hong Lim} and Arum Kim and Hong, {Jeong Ho} and Kim, {Jun Seok} and Koo, {Seung Hoi} and Lee, {Jae Seon} and Ko, {Young Gyu}",

note = "Funding Information: This work was supported by grants from the National Research Foundation of Korea awarded to; Y.-G. Ko (R1509597 and R20000552) and J.-S. Lee (R1A5A2031612). Publisher Copyright: {\textcopyright} 2022, The Author(s).",

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doi = "10.1038/s41467-022-33969-4",

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AU - Bahn, Myeong Suk

AU - Yu, Dong Min

AU - Lee, Myoungwoo

AU - Jo, Sung Je

AU - Lee, Ji Won

AU - Kim, Ho Chul

AU - Lee, Hyun

AU - Kim, Hong Lim

AU - Kim, Arum

AU - Hong, Jeong Ho

AU - Kim, Jun Seok

AU - Koo, Seung Hoi

AU - Lee, Jae Seon

AU - Ko, Young Gyu

N1 - Funding Information: This work was supported by grants from the National Research Foundation of Korea awarded to; Y.-G. Ko (R1509597 and R20000552) and J.-S. Lee (R1A5A2031612). Publisher Copyright: © 2022, The Author(s).

PY - 2022/12

Y1 - 2022/12

N2 - 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.

AB - 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.

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Central role of Prominin-1 in lipid rafts during liver regeneration

Abstract

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