PPARδ modulates oxLDL-induced apoptosis of vascular smooth muscle cells through a TGF-β/FAK signaling axis

The International Journal of Biochemistry & Cell Biology
Jung Seok HwangHan Geuk Seo

Abstract

The peroxisome proliferator-activated receptor delta (PPARδ) has been implicated in the modulation of vascular homeostasis. However, its roles in the apoptotic cell death of vascular smooth muscle cells (VSMCs) are poorly understood. Here, we demonstrate that PPARδ modulates oxidized low-density lipoprotein (oxLDL)-induced apoptosis of VSMCs through the transforming growth factor-β (TGF-β) and focal adhesion kinase (FAK) signaling pathways. Activation of PPARδ by GW501516, which is a specific ligand, significantly inhibited oxLDL-induced cell death and generation of reactive oxygen species in VSMCs. These inhibitory effects were significantly reversed in the presence of small interfering (si)RNA against PPARδ, or by blockade of the TGF-β or FAK signaling pathways. Furthermore, PPARδ-mediated recovery of FAK phosphorylation suppressed by oxLDL was reversed by SB431542, a specific ALK5 receptor inhibitor, indicating that a TGF-β/FAK signaling axis is involved in the action of PPARδ. Among the protein kinases activated by oxLDL, p38 mitogen-activated protein kinase was suppressed by ligand-activated PPARδ. In addition, oxLDL-induced expression and translocation of pro-apoptotic or anti-apoptotic factors were markedly affected in t...Continue Reading

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Citations

Sep 18, 2016·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Adeline PécheryIsabelle Lascombe
Jun 13, 2019·Journal of Experimental & Clinical Cancer Research : CR·Jin ZhouLiling Tang
May 11, 2019·International Journal of Hypertension·Yanli JiangZhencheng Yan
May 11, 2021·PPAR Research·Tao YangKamil Can Kural

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