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Gastrin-releasing peptide promotes the migration of vascular smooth muscle cells through upregulation of matrix metalloproteinase-2 and -9
Hyun-Joo Park1,#, Mi-Kyoung Kim1,#, Yeon Kim1, Sun Sik Bae2, Hyung Joon Kim1, Soo-Kyung Bae1, Moon-Kyoung Bae1,*
1School of Dentistry and 2Pusan National University School of Medicine, Pusan National University
Abstract
Gastrin-releasing peptide (GRP) has been reported to be implicated in the pathogenesis of inflammatory disorders. The migration and proliferation of vascular smooth muscle cells (VSMCs) are key components of vascular inflammation that leads to the development of atherosclerosis. The present study aimed to investigate the molecular effect of GRP on VSMC proliferation and migration. We report that GRP significantly enhanced the proliferation and migration of rat VSMCs. GRP increased mRNA and protein expression of matrix metalloproteinase-2 and -9 (MMP-2/9) in VSMCs. The induction of MMP-2/9 by GRP was regulated by the activation of the signal transducer and activator of transcription-3 (STAT-3). In addition, STAT3-knockdown of VSMCs by siRNA or blockade of the GRP receptor inhibited GRP-induced migration of VSMCs. Taken together, our findings indicate that GRP promotes the migration of VSMCs through upregulation of MMP-2/9 via STAT3 activation.
Abstract, Accepted Manuscript(in press) [Submitted on August 14, 2017, Accepted on October 11, 2017]
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