MG132 Induces Expression of Monocyte Chemotactic Protein‐Induced Protein 1 in Vascular Smooth Muscle Cells. Issue 1 (14th April 2016)

• Record Type: Journal Article
• Authors: Tan, Xi; Gao, Jie; Shi, Zhan; Tai, Shi; Chan, Leona Loretta; Yang, Yang; Peng, Dao‐Quan; Liao, Duan‐Fang; Jiang, Zhi‐Sheng; Chang, Ying‐Zi; Gui, Yu; Zheng, Xi‐Long
• Is Part Of: Journal of cellular physiology. Volume 232:Issue 1(2017:Jan.)
• Page Start: 122
• Page End: 128
• Publication Date: 2016-04-14
• Subjects: Physiology -- Periodicals; Cell physiology -- Periodicals; 571.6
• DOI: 10.1002/jcp.25396
• Languages: English
• ISSNs: 0021-9541

Abstract

Abstract : Monocyte chemoattractant protein‐1 (MCP‐1) has been reported to induce the expression of monocyte chemotactic protein‐induced protein 1 (MCPIP1), which undergoes ubiquitination degradation. Therefore, we predict that in vascular smooth muscle (VSMCs), MCPIP1 may be induced by MCP‐1 and undergo degradation, which can be inhibited by the proteasome inhibitor, MG132. Our results showed that treatment of human VSMCs with MCP‐1 did not increase the expression of MCPIP1. Treatment with MG132, however, elevated MCPIP1 protein levels through stimulation of the gene transcription, but not through increasing protein stability. MCPIP1 expression induced by MG132 was inhibited by α‐amanitin inhibition of gene transcription or cycloheximide inhibition of protein synthesis. Our further studies showed that MCPIP1 expression induced by MG132 was inhibited by the inhibitors of AKT and p38 kinase, suggesting a role of the AKT‐p38 pathway in MG132 effects. We also found that treatment with MG132 induces apoptosis, but overexpression of MCPIP1 inhibited bromodeoxyuridine (BrdU) incorporation of human VSMCs without induction of significant apoptosis. In summary, MCPIP1 expression is induced by MG132 likely through activation of the AKT‐p38 pathway. MCPIP1 inhibits SMC proliferation without induction of apoptosis. J. Cell. Physiol. 232: 122–128, 2017. © 2016 Wiley Periodicals, Inc. Abstract : Monocyte chemoattractant protein‐1 (MCP‐1) has been reported to induce the expression of monocyte chemotactic protein‐induced protein 1 (MCPIP1), which undergoes ubiquitination degradation. In cultured human vascular smooth muscle, MCPIP1 expression is induced by MG132, a proteasome inhibitor, through signal transduction and gene transcription. Overexpression of MCPIP1 results in inhibition of smooth muscle cell proliferation.