Inhibition of IL-8-mediated endothelial adhesion, VSMCs proliferation and migration by siRNA-TMEM98 suggests TMEM98’s emerging role in atherosclerosis
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Guangxin Lv1, Hongmei Zhu1, Cai Li1, Jingyu Wang1, Dandan Zhao1, Shuyao Li1, Le Ma2, Guohua Sun3, Fang Li4, Ying Zhao5 and Ying Gao1,5
1Department of Biochemistry and Molecular Biology, Dalian Medical University, Dalian, 116044, China
2College of Stomatology, Dalian Medical University, Dalian, 116044, China
3Department of Clinical Laboratory, The First Affiliated Hospital of Dalian Medical University, Dalian, 116044, China
4Department of Immunology, Dalian Medical University, Dalian, 116044, China
5Liaoning Provincial Core Lab of Medical Molecular Biology, Dalian Medical University, Dalian, 116044, China
Ying Gao, email: [email protected]
Ying Zhao, email: [email protected]
Keywords: atherosclerosis, IL-8, TMEM98, EC adhesion, VSMC proliferation and migration
Received: July 18, 2017 Accepted: September 03, 2017 Published: September 30, 2017
Transmembrane protein 98 (TMEM98), known as a novel gene related to lung cancer, hepatocellular carcinoma, differentiation of T helper 1 cells and normal eye development, has no defined role reported in terms of atherosclerosis (AS). To investigate the potential involvement of TMEM98 during AS processes, its obvious secretion and expression has been initially characterized in hyperlipidemia patients’ serum and AS mice’s serum respectively. We then explored the possible role of TMEM98 in the pathogenesis of AS in vitro. IL-8, a pro-atherogenesis cytokine, was used to induce the expression of TMEM98 in both endothelial cells (ECs) and vascular smooth muscle cells (VSMCs). Collectively, TMEM98 expression significantly increased in ECs and VSMCs, both induced by IL-8. Additionally, the adhesion ability of monocytes to ECs as well as the proliferation and migration of VSMCs were all decreased after siRNA-TMEM98 treatment. Furthermore, siRNA-TMEM98 dramatically inhibited the expression of ICAM-1 in ECs and the expression of p-AKT, p-GSK3β and Cyclin D1 from VSMCs, and AKT agonist partially restored the proliferation and migration of VSMC after siRNA-TMEM98 treatment. Taken together, siRNA-TMEM98 inhibits IL-8 mediated EC adhesion by down-regulating the expression of ICAM-1. Additionally, it also hinders the proliferation and migration of VSMCs through suppressing the AKT/GSK3β/Cyclin D1 signaling pathway. Our study provides sufficient evidence to support that TMEM98 could be a novel gene associated with AS for the first time.
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