Anti-inflammatory and anti-proliferative action of adiponectin mediated by insulin signaling cascade in human vascular smooth muscle cells

Eugenio Cersosimo, Xiaojing Xu, Tomoko Terasawa, Lily Q. Dong

Research output: Contribution to journalArticle

Abstract

After confirmation of the presence of adiponectin (ADPN) receptors and intra-cellular binding proteins in coronary artery smooth muscle cells (VSMC), we tested the hypotheses that, in acute insulin resistance: (i) the activation/inactivation of metabolic and mitogenic insulin signaling pathways are inversely affected by ADPN and, (ii) changes in VSMC migration/proliferation rates correlate with signal activity/inactivity. In primary cultures of VSMC exposed to high glucose and palmitate plus insulin, the expression of PI-3 kinase (Akt and m-TOR), MAP-Kinase (Erk and p-38) molecules, and inflammatory markers (TLR-4 and IkB-α) were assessed with Western blot, in the absence/presence of AdipoRon (AR). Migration and proliferation rates were measured in similar experimental conditions. There were decreases of ~ 25% (p-Akt) and 40–60% (p-mTOR) expressions with high glucose/palmitate, which reversed when AR was added were. Elevations in p-Erk and p-p38 expressions were obliterated by AR. Although, no changes were detected with high glucose and palmitate, when AR was added, a decline in inflammatory activity was substantiated by a ~ 50% decrease in TLR-4 and 40–60% increase in IkBα expression. Functional assays showed 10–20% rise in VSMC proliferation with high glucose and palmitate, but addition of AR lead to 15–25% decline. The degree of VSMC migration was reduced with AR addition by ~ 15%, ~ 35% and 55%, in VSMC exposed to 5 mM, 25 mM glucose and 25 mM + 200 µM palmitate, respectively. Changes in intracellular molecular messaging in experiments mimicking acute insulin resistance suggest that anti-inflammatory and anti-atherogenic actions of ADPN in VSMC are mediated via insulin signaling pathways.

Original languageEnglish (US)
Pages (from-to)6561-6572
Number of pages12
JournalMolecular Biology Reports
Volume47
Issue number9
DOIs
StatePublished - Sep 1 2020

Keywords

  • Adiponectin
  • Arterial smooth muscle cells
  • Cell migration & proliferation
  • Hyperinsulinemia
  • Inflammation
  • Insulin resistance
  • Insulin signaling

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics

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