Xu X.,Nantong University |
Xu X.,Key Laboratory of Inflammation and Molecular Drug Target |
He M.,Nantong University |
He M.,Key Laboratory of Inflammation and Molecular Drug Target |
And 6 more authors.
Cellular Physiology and Biochemistry | Year: 2015
Background/Aims: salusin-β 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 (PPARγ) exerts a vascular protective role beyond its metabolic effects. Salusin-β has direct effects on VSMCs. The aim of the present study was to assess the effect of salusin-β on PPARγ 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-α (TNF-α) were determined using enzyme-linked immunosorbent assay. Results: Salusin-β negatively regulated PPARγ gene expression at protein, mRNA and gene promoter level in VSMCs. The inhibitory effect of salusin-β on PPARγ gene expression contributed to salusin-β-induced VSMCs proliferation and inflammation in vitro. IκBα-NF-κB activation, but not NF-κB p50 or p65, mediated the salusin-β-induced inhibition of PPARγ gene expression. Salusin-β induced nuclear translocation of histone deacetylase 3 (HDAC3). HDAC3 siRNA prevented salusin-β-induced PPARγ reduction. Nuclear translocation of HDAC3 in response to salusin-β was significantly reversed by an IκBα inhibitor BAY 11-7085. Furthermore, IκBα-HDAC3 complex was present in the cytosol of VSMCs but interrupted after salusin-β treatment. Conclusion: IκBα-HDAC3 pathway may contribute to salusin-β-induced inhibition of PPARγ gene expression in VSMCs. Copyright © 2015 S. Karger AG, Basel.