title: Kif4 regulates the expression of VEGFR1 through the PI3K/Akt signaling pathway in RAW264.7 monocytes/macrophages.
abstract: Kinesin superfamily protein 4 (Kif4), a microtubule-based motor protein, has been shown to participate in a number of critical cellular processes, such as cell division, the intracellular transport of membranous vesicles and signal transduction. However, whether KIF4 regulates vascular endothelial growth factor (VEGF) receptor 1 (VEGFR1) expression remains unknown. Thus, in this study, in order to examine the effects of Kif4 on the expression of VEGFR1 in RAW264.7 monocytes/macrophages, Kif4 was silenced using siRNA. RT-qPCR, western blot analysis and ELISA were used to assess the expression of Kif4 and VEGFR1 up- and downstream signaling molecules, including VEGF-A, VEGFR1, soluble form of VEGFR1 (sVEGFR1), phosphorylated (p-)Akt and Akt. The silencing Kif4 inhibited the mRNA expression of VEGF (P<0.01) and p-Akt (P<0.05); however, the level of VEGF-A was increased (P<0.05) compared with the negative control siRNA-transfected group. The silencing of Kif4 decreased the VEGFR1 mRNA (P<0.05), VEGFR1 protein and sVEGFR1 levels in the cell supernatant (P<0.01). Following the application of insulin-like growth factor-1 (100 ng/ml), the specific agonist of PI3K/Akt in the Kif4 siRNA-transfected group, the VEGFR1 mRNA levels (P<0.001), the VEGFR1 protein levels and the sVEGFR1 (P<0.01) levels significantly increased; however, the levels of VEGF in the cell supernatant were decreased (P<0.05). Taken together, these findings suggest that Kif4 regulates the expression of VEGFR1 in RAW264.7 cells and that the PI3K/Akt pathway is involved in this process.
authors.affiliation: Department of Stomatology and Institute of Stomatology, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Stomatology and Institute of Stomatology, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China.
authors.forename: Yijun
authors.initials: Y
authors.lastname: Luan
authors.affiliation: Department of Stomatology and Institute of Stomatology, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China.
authors.forename: Shaohua
authors.initials: S
authors.lastname: Liu
authors.affiliation: Institute of Basic Medical Sciences and Key Laboratory of Cardiovascular Proteomics, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China.
authors.forename: Jintang
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Stomatology and Institute of Stomatology, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China.
authors.forename: Ketao
authors.initials: K
authors.lastname: Wang
authors.affiliation: Jinan Stomalogic Hospital, Jinan, Shandong 250012, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Cai
authors.affiliation: Department of Biomedical Science, The University of Sheffield, Sheffield S10 2TN, UK.
authors.forename: Wen
authors.initials: W
authors.lastname: Jiang
authors.affiliation: School of Stomatology, Shandong University, Jinan, Shandong 250012, P.R. China.
authors.forename: Pishan
authors.initials: P
authors.lastname: Yang
authors.affiliation: Department of Stomatology and Institute of Stomatology, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China.
authors.forename: Fengcai
authors.initials: F
authors.lastname: Wei
authors.affiliation: Department of Stomatology and Institute of Stomatology, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China.
authors.forename: Xun
authors.initials: X
authors.lastname: Qu
mesh_terms: D000818:Animals; D002460:Cell Line; D005786:Gene Expression Regulation / Q000187:drug effects; D020868:Gene Silencing; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D016547:Kinesins / Q000235:genetics / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics*
chemical_list: D007334:Insulin-Like Growth Factor I; D016547:Kinesins; D035683:MicroRNAs; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1; C089655:Kif4 protein, mouse