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- Title
Ligand-Activated Peroxisome Proliferator-Activated Receptor δ Attenuates Vascular Oxidative Stress by Inhibiting Thrombospondin-1 Expression.
- Authors
Ahn, Min Young; Ham, Sun Ah; Yoo, Taesik; Lee, Won Jin; Hwang, Jung Seok; Paek, Kyung Shin; Lim, Dae-Seog; Han, Sung Gu; Lee, Chi-Ho; Seo, Han Geuk
- Abstract
Thrombospondin-1 (TSP-1) is implicated in vascular diseases associated with oxidative stress, such as abdominal aortic aneurysms, ischemia-reperfusion injury, and atherosclerosis. However, the regulatory mechanisms underlying TSP-1 expression are not fully elucidated. In this study, we found that peroxisome proliferator-activated receptor δ (PPARδ) inhibited oxidative stress-induced TSP-1 expression and migration in vascular smooth muscle cells (VSMCs). Activation of PPARδ by GW501516, a specific ligand for PPARδ, significantly attenuated hydrogen peroxide (H2O2)-induced expression of TSP-1 in VSMCs. Small interfering RNA-mediated knockdown of PPARδ and treatment with GSK0660, a selective PPARδ antagonist, reversed the effect of GW501516 on H2O2-induced expression of TSP-1, suggesting that PPARδ is associated with GW501516 activity. Furthermore, JNK (c-Jun N-terminal kinase), but not p38 and ERK (extracellular signal-regulated kinase), mediated PPARδ-dependent inhibition of TSP-1 expression in VSMCs exposed to H2O2. GW501516- activated PPARδ also reduced the H2O2-induced generation of reactive oxygen species, concomitant with inhibition of VSMC migration. In particular, TSP-1 contributed to the action of PPARδ in the regulation of H2O2-induced interleukin-1β expression. These results suggest that PPARδ-modulated downregulation of TSP-1 is associated with reduced cellular oxidative stress, thereby inhibiting H2O2-induced phenotypic changes in vascular cells.
- Subjects
LIGANDS (Biochemistry); PEROXISOMES; OXIDATIVE stress; THROMBOSPONDIN-1; AORTIC aneurysms
- Publication
Journal of Vascular Research, 2018, Vol 55, Issue 2, p75
- ISSN
1018-1172
- Publication type
Article
- DOI
10.1159/000486570