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Updated: Jun 5, 2026

A High-Throughput Luciferase Assay to Evaluate Proteolysis of the Single-Turnover Protease PCSK9
08:14

A High-Throughput Luciferase Assay to Evaluate Proteolysis of the Single-Turnover Protease PCSK9

Published on: August 28, 2018

Janus kinase activation by cytokine oncostatin M decreases PCSK9 expression in liver cells

Aiqin Cao1, Minhao Wu, Hai Li

  • 1Department of Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USA.

Journal of Lipid Research
|January 4, 2011
PubMed

Insights

Oncostatin M (OM) suppresses PCSK9 expression, a novel mechanism for lowering LDL cholesterol. This cytokine-mediated pathway involves JAKs and ERK signaling, offering new therapeutic targets for hypercholesterolemia.

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Cardiovascular Research

Background:

  • Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates LDL cholesterol by degrading the LDL receptor (LDLR).
  • Inhibiting PCSK9 expression presents a therapeutic strategy for hypercholesterolemia.
  • Oncostatin M (OM) was previously shown to activate LDLR gene transcription.

Purpose of the Study:

  • To investigate the effect of Oncostatin M (OM) on PCSK9 expression.
  • To elucidate the signaling pathways involved in OM-mediated regulation of PCSK9.
  • To validate the in vivo relevance of OM's effect on PCSK9 in hypercholesterolemia.

Main Methods:

  • HepG2 cells were treated with OM to assess PCSK9 mRNA and protein levels.
  • Inhibition studies and siRNA depletion were used to identify key signaling molecules (JAK1, JAK2, STATs, ERK).
  • In vivo studies in hypercholesterolemic hamsters utilized an anti-PCSK9 antibody to measure liver PCSK9 expression.

Main Results:

  • OM treatment significantly decreased PCSK9 mRNA and protein levels in HepG2 cells.
  • JAK1 and JAK2 were identified as critical mediators of OM's inhibitory effect on PCSK9.
  • Sustained ERK pathway activation, but not STAT signaling, was essential for OM's PCSK9 suppression.
  • In vivo, OM suppressed liver PCSK9 expression in hypercholesterolemic hamsters.

Conclusions:

  • OM suppresses PCSK9 expression through a mechanism involving JAKs and the ERK signaling pathway.
  • This cytokine-triggered regulatory network provides a novel target for cholesterol-lowering therapies.
  • OM's dual action on LDLR (transcription activation and PCSK9 suppression) enhances LDL uptake.

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