Effect of Salusin-β on Peroxisome Proliferator-Activated Receptor Gamma Gene Expression in Vascular Smooth Muscle Cells and its Possible Mechanism

Background/Aims: salusin-beta is considered to be a potential pro-atherosclerotic factor. Regulation and function of vascular smooth muscle cells (VSMCs) are important in the progression of atherosclerosis. Peroxisome proliferator-activated receptor gamma (PPAR gamma) exerts a vascular protective role beyond its metabolic effects. Salusin-beta has direct effects on VSMCs. The aim of the present study was to assess the effect of salusin-beta on PPAR gamma gene expression in primary cultured rat VSMCs. Methods: Western blotting analysis, real-time PCR and transient transfection approach were used to determine expression of target proteins. Specific protein knockdown was performed with siRNA transfection. Cell proliferation was determined by 5-bromo-2'-deoxyuridine incorporation. The levels of inflammation indicators interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) were determined using enzyme-linked immunosorbent assay. Results: Salusin-beta negatively regulated PPAR. gene expression at protein, mRNA and gene promoter level in VSMCs. The inhibitory effect of salusin-beta on PPAR gamma gene expression contributed to salusin-beta-induced VSMCs proliferation and inflammation in vitro. I kappa B alpha-NF-kappa B activation, but not NF-kappa B p50 or p65, mediated the salusin-beta-induced inhibition of PPAR gamma gene expression. Salusin-beta induced nuclear translocation of histone deacetylase 3 (HDAC3). HDAC3 siRNA prevented salusin-beta-induced PPAR gamma reduction. Nuclear translocation of HDAC3 in response to salusin-beta was significantly reversed by an I kappa B alpha inhibitor BAY 11-7085. Furthermore, I kappa B alpha-HDAC3 complex was present in the cytosol of VSMCs but interrupted after salusin-beta treatment. Conclusion: I kappa B alpha-HDAC3 pathway may contribute to salusin-beta-induced inhibition of PPAR gamma gene expression in VSMCs. Copyright (C) 2015 S. Karger AG, Basel