Abstract
Regeneration is a unique defense mechanism of liver tissue in response to functional cell loss induced by toxic chemicals or surgical resection. In this study, we found that Islet-cell autoantigen 69 (Ica69) accelerates liver regeneration in mice. Following 70% partial hepatectomy, both Ica69 mRNA and protein are significantly upregulated in mouse hepatocytes at the early stage of liver regeneration. Compared with the wild-type mice, Ica69-deficient mice have more severe liver injury, delayed liver regeneration, and high surgical accidental mortality following hepatectomy. Mechanistically, Ica69 interacts with Pick1 protein to regulate Tgfbr1 protein expression and Tgfβ-induced Smad2 phosphorylation. Our findings suggest that Ica69 in liver tissue is a new potential target for promoting liver regeneration.
Keywords:
ICA69; PICK1; TGFBRI; Tgfβ signaling; hepatocyte; liver regeneration.
© 2020 Federation of European Biochemical Societies.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Autoantigens / genetics*
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Autoantigens / metabolism
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Binding Sites
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Cell Cycle Proteins / genetics
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Cell Cycle Proteins / metabolism
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Gene Expression Regulation
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Hepatectomy / methods
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Hepatocytes / cytology
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Hepatocytes / drug effects
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Hepatocytes / metabolism*
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Liver / cytology
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Liver / metabolism*
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Liver / surgery
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Liver Regeneration / genetics*
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Male
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Phosphorylation / drug effects
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Primary Cell Culture
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Protein Binding
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Receptor, Transforming Growth Factor-beta Type I / genetics*
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Receptor, Transforming Growth Factor-beta Type I / metabolism
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Signal Transduction
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Smad2 Protein / genetics
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Smad2 Protein / metabolism
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Transforming Growth Factor beta / genetics*
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Transforming Growth Factor beta / metabolism
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Transforming Growth Factor beta / pharmacology
Substances
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Autoantigens
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Cell Cycle Proteins
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Ica1 protein, mouse
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Prkcabp protein, mouse
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Smad2 Protein
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Smad2 protein, mouse
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Transforming Growth Factor beta
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Receptor, Transforming Growth Factor-beta Type I
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Tgfbr1 protein, mouse