Kif4 regulates the expression of VEGFR1 through the PI3K/Akt signaling pathway in RAW264.7 monocytes/macrophages

Xu,Yan; Luan,Yijun; Liu,Shaohua; Sun,Jintang; Wang,Ketao; Cai,Jun; Jiang,Wen; Yang,Pishan; Wei,Fengcai; Qu,Xun

doi:10.3892/ijmm.2017.2936

Kif4 regulates the expression of VEGFR1 through the PI3K/Akt signaling pathway in RAW264.7 monocytes/macrophages

Authors:
- Yan Xu
- Yijun Luan
- Shaohua Liu
- Jintang Sun
- Ketao Wang
- Jun Cai
- Wen Jiang
- Pishan Yang
- Fengcai Wei
- Xun Qu
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Affiliations: Department of Stomatology and Institute of Stomatology, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China, Institute of Basic Medical Sciences and Key Laboratory of Cardiovascular Proteomics, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China, Jinan Stomalogic Hospital, Jinan, Shandong 250012, P.R. China, Department of Biomedical Science, The University of Sheffield, Sheffield S10 2TN, UK, School of Stomatology, Shandong University, Jinan, Shandong 250012, P.R. China
Published online on: March 27, 2017 https://doi.org/10.3892/ijmm.2017.2936
Pages: 1285-1290

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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.

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