PMID- 30585263 OWN - NLM STAT- MEDLINE DCOM- 20190909 LR - 20200309 IS - 1449-2288 (Electronic) IS - 1449-2288 (Linking) VI - 14 IP - 14 DP - 2018 TI - SAK-HV Promotes RAW264.7 cells Migration Mediated by MCP-1 via JNK and NF-kappaB Pathways. PG - 1993-2002 LID - 10.7150/ijbs.27459 [doi] AB - 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-kappaB (NF-kappaB) 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-kappaB 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-kappaB 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. FAU - Chen, Yao AU - Chen Y AD - Institute of Military Cognitive and Brain Sciences, Beijing, 100850, China. FAU - Fu, Wen-Liang AU - Fu WL AD - Institute of Military Cognitive and Brain Sciences, Beijing, 100850, China. FAU - Gan, Xiang-Dong AU - Gan XD AD - Institute of Military Cognitive and Brain Sciences, Beijing, 100850, China. FAU - Xing, Wei-Wei AU - Xing WW AD - Institute of Military Cognitive and Brain Sciences, Beijing, 100850, China. FAU - Xia, Wen-Rong AU - Xia WR AD - Institute of Military Cognitive and Brain Sciences, Beijing, 100850, China. FAU - Zou, Min-Ji AU - Zou MJ AD - Institute of Military Cognitive and Brain Sciences, Beijing, 100850, China. FAU - Liu, Qing AU - Liu Q AD - Institute of Military Cognitive and Brain Sciences, Beijing, 100850, China. FAU - Wang, Yuan-Yuan AU - Wang YY AD - Institute of Military Cognitive and Brain Sciences, Beijing, 100850, China. FAU - Zhang, Chao AU - Zhang C AD - Division of Oncology Research, Mayo Clinic, Rochester, MN 55905, USA. FAU - Xu, Dong-Gang AU - Xu DG AD - Institute of Military Cognitive and Brain Sciences, Beijing, 100850, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20181102 PL - Australia TA - Int J Biol Sci JT - International journal of biological sciences JID - 101235568 RN - 0 (Ccr2 protein, mouse) RN - 0 (Chemokine CCL2) RN - 0 (NF-kappa B) RN - 0 (RNA, Small Interfering) RN - 0 (Receptors, CCR2) RN - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) SB - IM MH - Animals MH - Cell Movement/genetics/*physiology MH - Chemokine CCL2/genetics/*metabolism MH - Enzyme-Linked Immunosorbent Assay MH - JNK Mitogen-Activated Protein Kinases/genetics/metabolism MH - Macrophages/metabolism MH - Male MH - Mice MH - Mitogen-Activated Protein Kinases/genetics/metabolism MH - NF-kappa B/genetics/metabolism MH - Phosphorylation/genetics/physiology MH - RAW 264.7 Cells MH - RNA, Small Interfering/genetics MH - Receptors, CCR2/genetics MH - Signal Transduction/genetics/physiology MH - Transfection MH - Wound Healing/genetics/physiology PMC - PMC6299369 OTO - NOTNLM OT - JNK OT - MCP-1 OT - NF-kappaB OT - SAK-HV OT - macrophage migration COIS- Competing Interests: The authors have declared that no competing interest exists. EDAT- 2018/12/27 06:00 MHDA- 2019/09/10 06:00 PMCR- 2018/01/01 CRDT- 2018/12/27 06:00 PHST- 2018/05/24 00:00 [received] PHST- 2018/09/25 00:00 [accepted] PHST- 2018/12/27 06:00 [entrez] PHST- 2018/12/27 06:00 [pubmed] PHST- 2019/09/10 06:00 [medline] PHST- 2018/01/01 00:00 [pmc-release] AID - ijbsv14p1993 [pii] AID - 10.7150/ijbs.27459 [doi] PST - epublish SO - Int J Biol Sci. 2018 Nov 2;14(14):1993-2002. doi: 10.7150/ijbs.27459. eCollection 2018.