STRIP2 silencing inhibits vascular smooth muscle cell proliferation and migration via P38–AKT–MMP‐2 signaling pathway

Abstract

STRIP2 (FAM40B) was reported to regulate tumor cell migration. Our study aims to discuss the effect of STRIP2 in mouse aortic smooth muscle cell (MOVAS) proliferation and migration processes, which contributes greatly to atherosclerosis formation. In MOVAS cells, STRIP2 depletion suppressed cell proliferation and migration, which were related to a remarkable decrease in matrix metalloproteinases-2 (MMP-2)/MMP-9 expression. Additionally, P38 mitogen-activated protein kinases and Protein kinase B (AKT) are inactivated while extracellular signal-regulated kinase (ERK1/2) and jun N-terminal kinase (JNK) are activated upon STRIP2 silencing. SB203580 (P38 inhibitor) further reduced AKT phosphorylation (p-AKT) while dehydrocorydaline chloride (Dc; P38 activator) reversed this effect. Furthermore, Dc significantly recovered MMP-2 expression in STRIP2-knockdown cells. As expected, overexpressing STRIP2 exhibited a contrary effect. Dc and AKT activator SC79 reversed the inhibition of cell proliferation and migration induced by STRIP2 silencing. Interestingly, STRIP2 depletion increased vascular endothelial growth factor level significantly. Taken together, STRIP2 contributed to cell proliferation and migration through P38-AKT-MMP-2 signaling in MOVAS cells, indicating the importance of STRIP2 in atherosclerosis. K E Y W O R D S cell proliferation and migration, MMP-2, MOVAS, P38, STRIP2

STRIP2, a member of the striatin‐interacting phosphatase and kinase complex, is implicated in lung adenocarcinoma cell growth and migration

“…However, a few articles reported that STRIP2 was involved in the modulation of the Akt/mTOR pathway. The deficiency of STRIP2 has been illustrated to restrain the proliferation and migration of vascular smooth muscle cells through affecting the Akt pathway . In line with the earlier reports, our article manifested that overexpression of STRIP2 promoted cell proliferation, which might be achieved by the activation of the Akt/mTOR pathway in LUAD cells.…”

“…Increasingly, dysregulation of STRIPAK components is involved in various diseases including cancer [9]. Striatin-interacting protein 2 (STRIP2), as one member of the STRIPAK complex and also called Fam40b, took part in regulating tumor cell growth and migration [10,11]. According to the research by Madsen et al [11], STRIP2 ablation lessened cell migration of breast cancer cells.…”

Inhibition of Soluble Epoxide Hydrolase in Macrophages Ameliorates the Formation of Foam Cells ― Role of Heme Oxygenase-1 ―

“…22 MMP-2 and -9 promote the development of atherosclerosis and are recognized as major factors in causing plaque destabilization. 23 The expression of MMP-2 and -9 were elevated in the ApoE −/− mice, while the present study data confirmed that both MMP-2 and -9 mRNA levels were normalized in response to TPPU treatment. Furthermore, the underlying molecular mechanism of TPPU on suppressing macrophages foam cell formation is mediated by reducing oxLDL internalization and elevating cholesterol efflux, rather than endogenous cholesterol synthesis.…”

Progress in the mechanism and targeted drug therapy for COPD

“…57 MMPs also play a role in vascular remodelling by modulating the migration and proliferation of smooth muscle cells and endothelial cells and mediating the release of the smooth muscle cell mitogens and growth factors, increasing the risk of COPD pulmonary hypertension. [58][59][60][61] The endogenous inhibitors of MMPs are tissue inhibitors of metalloproteinases (TIMPs). TIMPs are a family of low-molecular-weight proteins with four known members.…”