Hepatic Apolipoprotein M Suppresses Hepatocyte Secretion of Prothrombin by Upregulating Arid5B

Abstract

Background

Apolipoprotein M (ApoM) is a minor apolipoprotein bound to HDL, which carries sphingosine 1-phosphate (S1P), a potent lipid mediator.

Material and Methods

Since HDL has been proposed to possess pleiotropic effects, including an anti-thrombotic effect, we investigated the association between ApoM and coagulopathy.

Results

ApoM overexpression suppressed and ApoM knockout accelerated the decrease in platelet counts, but ApoM overexpression accelerated and ApoM knockout suppressed the prolongation of prothrombin time and activated partial thromboplastin time in a murine lipopolysaccharide-induced model of sepsis. ApoM decreased the plasma/culture-medium prothrombin levels and increased the hepatic/cellular prothrombin levels in mice and HepG2 cells, a hepatocyte cell line. S1P receptor knockdown did not inhibit prothrombin secretion by HepG2 cells.

Conclusion

An RNA-sequence-based approach suggested that Arid5B was involved in these effects of ApoM. Arid5B knockdown increased the culture-medium prothrombin level but decreased cellular prothrombin level. ApoM upregulated Arid5B, and Arid5B knockdown antagonized the inhibitory effect of ApoM on prothrombin secretion. Hepatic ApoM suppresses hepatocyte prothrombin secretion independent of S1P receptors, by upregulation of Arid5B.

Keywords

apolipoprotein M - HDL - sphingosine 1-phosphate - prothrombin - Arid5B

Data Availability Statement

All relevant data are presented within the paper, and the datasets generated or analyzed during this study will be made available upon reasonable request.

Publikationsverlauf

Eingereicht: 06. Januar 2024

Angenommen: 23. Juli 2025

Accepted Manuscript online:
24. Juli 2025

Artikel online veröffentlicht:
04. August 2025

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