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Int J Biol Sci 2018; 14(14):1993-2002. doi:10.7150/ijbs.27459

Research Paper

SAK-HV Promotes RAW264.7 cells Migration Mediated by MCP-1 via JNK and NF-κB Pathways

Yao Chen1, Wen-Liang Fu1, Xiang-Dong Gan1, Wei-Wei Xing1, Wen-Rong Xia1, Min-Ji Zou1, Qing Liu1, Yuan-Yuan Wang1, Chao Zhang2✉, Dong-Gang Xu1✉

1. Institute of Military Cognitive and Brain Sciences, Beijing, 100850, China.
2. Division of Oncology Research, Mayo Clinic, Rochester, MN 55905, USA.

Abstract

Macrophage migration plays an essential role in immune system and is also involved in many pathological situations. However, the regulatory mechanism of macrophage migration remains to be elucidated due to its diverse responses to various stimuli. SAK-HV, a multifunctional protein possessing thrombolytic and lipid-lowering activity, can selectively induce the macrophage proliferation. Here, we reported SAK-HV significantly triggered RAW264.7 cells migration through its functional domain of SAK-mutant by activating both c-jun N-terminal kinases (JNK) and nuclear factor-κB (NF-κB) pathways. Meanwhile, SAK-HV upregulated the expression of some effector proteins, among which only the expression of Monocyte chemoattractant protein-1 (MCP-1) was inhibited by the blockade of JNK and NF-κB pathways. Further research showed that MCP-1 promoted migration ultimately by interacting with Chemokine (C-C motif) Receptor 2 (CCR2) in an autocrine manner. In summary, SAK-HV induced RAW264.7 cells migration through its SAK-mutant domain, during which MCP-1 chemokine mediated by JNK and NF-κB pathways played a key role. These results revealed a novel effect of SAK-HV on modulating macrophage migration and also deepened the understanding of its pharmacodynamics.

Keywords: SAK-HV, macrophage migration, MCP-1, JNK, NF-κB

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
How to cite this article:
Chen Y, Fu WL, Gan XD, Xing WW, Xia WR, Zou MJ, Liu Q, Wang YY, Zhang C, Xu DG. SAK-HV Promotes RAW264.7 cells Migration Mediated by MCP-1 via JNK and NF-κB Pathways. Int J Biol Sci 2018; 14(14):1993-2002. doi:10.7150/ijbs.27459. Available from http://www.ijbs.com/v14p1993.htm