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.
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.
School of Biological Sciences and Technology, Chonnam National University, Gwangju 500-757, Republic of Korea.
Ki-Mo
KM
Lee
Haeng-A
HA
Kang
Min
M
Park
Hwa-Youn
HY
Lee
Ha-Rim
HR
Choi
Chul-Ho
CH
Yun
Jae-Wook
JW
Oh
Hyung-Sik
HS
Kang
D000818:Animals; D017209:Apoptosis; D015415:Biomarkers / Q000378:metabolism; D002478:Cells, Cultured; D005994:Glycerophosphates / Q000494:pharmacology; D006801:Humans; D007378:Interleukins / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D009131:Muscle, Smooth, Vascular; D010006:Osteoblasts / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D061205:Vascular Calcification / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D051153:Wnt Proteins / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism; D000099180:Interleukin-24
D015415:Biomarkers; D005994:Glycerophosphates; D007378:Interleukins; D051153:Wnt Proteins; D051176:beta Catenin; D000099180:Interleukin-24; C031463:beta-glycerophosphoric acid