TMEM98, a novel secretory protein, promotes endothelial cell adhesion as well as vascular smooth muscle cell proliferation and migration.

Abstract

Transmembrane protein 98 (TMEM98) is a novel gene, and its function has not been well investigated. In a prior study, we have shown that siRNA-mediated knockdown of TMEM98 inhibited interleukin-8 (IL-8) promoted endothelial cell (EC) adhesion, as well as vascular smooth muscle cell (VSMC) proliferation and migration in the vascular endothelial and smooth muscle cell dysfunction. Herein, we used gain- and loss-of-function approaches combined with biochemical techniques to further explore the role of TMEM98 in the vascular wall cell. The expression and secretion of TMEM98 was increased in cultured human umbilical vein endothelial cells (HUVECs) and VSMCs treated with IL-8 and platelet-derived growth factor-BB (PDGF-BB). Also, PDGF-BB secretion was increased in TMEM98-treated HUVECs and VSMCs. Thus, it appears that TMEM98 and PDGF-BB form a positive feedback loop in potentiation of EC adhesion, as well as VSMC proliferation and migration. Knockdown of TMEM98 mediated by siRNA inhibited PDGF-BB-promoted EC adhesion by downregulating the expression of ICAM-1 and VCAM-1, as well as impaired the proliferation and migration of VSMCs by suppressing the AKT/GSK3β/cyclinD1 signaling pathway and reducing the expression of β-catenin. Hence, TMEM98 promoted EC adhesion by inducing the expression of ICAM-1/VCAM-1 and triggered VSMC proliferation and migration by activating the ERK and AKT/GSK3β signaling pathways. Taken together, TMEM98 may serve as a potential therapeutic target for the clinical treatment of vascular endothelial and smooth muscle cell dysfunction.