Interleukin-24 attenuates β-glycerophosphate-induced calcification of vascular smooth muscle cells by inhibiting apoptosis, the expression of calcification and osteoblastic markers, and the Wnt/β-catenin pathway

Biochem Biophys Res Commun. 2012 Nov 9;428(1):50-5. doi: 10.1016/j.bbrc.2012.09.145. Epub 2012 Oct 11.

Abstract

Vascular calcification is a hallmark of cardiovascular disease. Interleukin-24 (IL-24) has been known to suppress tumor progression in a variety of human cancers. However, the role of IL-24 in the pathophysiology of diseases other than cancer is unclear. We investigated the role of IL-24 in vascular calcification. IL-24 was applied to a β-glycerophosphate (β-GP)-induced rat vascular smooth muscle cell (VSMC) calcification model. In this study, IL-24 significantly inhibited β-GP-induced VSMC calcification, as determined by von Kossa staining and calcium content. The inhibitory effect of IL-24 on VSMC calcification was due to the suppression of β-GP-induced apoptosis and expression of calcification and osteoblastic markers. In addition, IL-24 abrogated β-GP-induced activation of the Wnt/β-catenin pathway, which plays a key role in the pathogenesis of vascular calcification. The specificity of IL-24 for the inhibition of VSMC calcification was confirmed by using a neutralizing antibody to IL-24. Our results suggest that IL-24 inhibits β-GP-induced VSMC calcification by inhibiting apoptosis, the expression of calcification and osteoblastic markers, and the Wnt/ β-catenin pathway. Our study may provide a novel mechanism of action of IL-24 in cardiovascular disease and indicates that IL-24 is a potential therapeutic agent in VSMC calcification.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis*
  • Biomarkers / metabolism
  • Cells, Cultured
  • Glycerophosphates / pharmacology
  • Humans
  • Interleukins / antagonists & inhibitors
  • Interleukins / pharmacology
  • Interleukins / physiology*
  • Male
  • Muscle, Smooth, Vascular
  • Osteoblasts / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Vascular Calcification / chemically induced
  • Vascular Calcification / metabolism*
  • Vascular Calcification / pathology
  • Wnt Proteins / metabolism
  • beta Catenin / metabolism

Substances

  • Biomarkers
  • Glycerophosphates
  • Interleukins
  • Wnt Proteins
  • beta Catenin
  • interleukin-24
  • beta-glycerophosphoric acid