Nesfatin-1 promotes VSMC migration and neointimal hyperplasia by upregulating matrix metalloproteinases and downregulating PPARγ

• Published in: Biomedicine & pharmacotherapy 2018-06, Vol.102, p.711-717
• Main Authors: Zhang, Ji-Ru, Lu, Qing-Bo, Feng, Wu-Bing, Wang, Hui-Ping, Tang, Zi-Han, Cheng, Han, Du, Qiong, Wang, Yuan-Ben, Li, Ke-Xue, Sun, Hai-Jian
• Format: Article
• Language: English
• Subjects: Animals; Calcium-Binding Proteins - metabolism; Cell Dedifferentiation; Cell Movement; Cell Proliferation; DNA-Binding Proteins - metabolism; Down-Regulation; Gene Silencing; Hyperplasia; Male; Matrix metalloproteinase; Matrix Metalloproteinase 2 - metabolism; Matrix Metalloproteinase 9 - metabolism; Matrix Metalloproteinases - metabolism; Migration; Muscle, Smooth, Vascular - cytology; Myocytes, Smooth Muscle - cytology; Myocytes, Smooth Muscle - enzymology; Neointima - metabolism; Neointima - pathology; Nerve Tissue Proteins - metabolism; Phenotype; PPAR gamma - metabolism; Proliferation; Rats, Sprague-Dawley; Up-Regulation; Vascular smooth muscle cells
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2018.03.120

[Display omitted] •Nesfatin-1 promoted VSMC phenotype switch from contractile to synthetic state.•Nesfatin-1 stimulated VSMC proliferation and migration.•MMP2/MMP-9 and PPARγ participated in the action of nesfatin-1.•Knockdown of nesfatin-1 ameliorated neointima formation after carotid injury. The dedifferentiation, proliferation and migration of vascular smooth muscle cells (VSMCs) are essential in the progression of hypertension, atherosclerosis and intimal hyperplasia. Nesfatin-1 is a potential modulator in cardiovascular functions. However, the role of nesfatin-1 in VSMC biology has not been explored. The present study was designed to determine the regulatory role of nesfatin-1 in VSMC proliferation, migration and intimal hyperplasia after vascular injury. Herein, we demonstrated that nesfatin-1 promoted VSMC phenotype switch from a contractile to a synthetic state, stimulated VSMC proliferation and migration in vitro. At the molecular level, nesfatin-1 upregulated the protein and mRNA levels, as well as the promoter activities of matrix metalloproteinase 2 (MMP-2) and MMP-9, but downregulated peroxisome proliferator-activated receptor γ (PPARγ) levels and promoter activity in VSMCs. Blockade of MMP-2/9 or activation of PPARγ prevented the nesfatin-1-induced VSMC proliferation and migration. In vivo, knockdown of nesfatin-1 ameliorated neointima formation following rat carotid injury. Taken together, our results indicated that nesfatin-1 stimulated VSMC proliferation, migration and neointimal hyperplasia by elevating MMP2/MMP-9 levels and inhibiting PPARγ gene expression.