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Article

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
  • View Affiliations / Copyright

    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
  • Pages: 1285-1290
    |
    Published online on: March 27, 2017
       https://doi.org/10.3892/ijmm.2017.2936
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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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1 

Hirokawa N, Noda Y, Tanaka Y and Niwa S: Kinesin super-family motor proteins and intracellular transport. Nat Rev Mol Cell Biol. 10:682–696. 2009. View Article : Google Scholar : PubMed/NCBI

2 

Lawrence CJ, Dawe RK, Christie KR, Cleveland DW, Dawson SC, Endow SA, Goldstein LS, Goodson HV, Hirokawa N, Howard J, et al: A standardized kinesin nomenclature. J Cell Biol. 167:19–22. 2004. View Article : Google Scholar : PubMed/NCBI

3 

Sekine Y, Okada Y, Noda Y, Kondo S, Aizawa H, Takemura R and Hirokawa N: A novel microtubule-based motor protein (KIF4) for organelle transports, whose expression is regulated developmentally. J Cell Biol. 127:187–201. 1994. View Article : Google Scholar : PubMed/NCBI

4 

Kurasawa Y, Earnshaw WC, Mochizuki Y, Dohmae N and Todokoro K: Essential roles of KIF4 and its binding partner PRC1 in organized central spindle midzone formation. EMBO J. 23:3237–3248. 2004. View Article : Google Scholar : PubMed/NCBI

5 

Zhu C and Jiang W: Cell cycle-dependent translocation of PRC1 on the spindle by Kif4 is essential for midzone formation and cytokinesis. Proc Natl Acad Sci USA. 102:343–348. 2005. View Article : Google Scholar :

6 

Wu G, Zhou L, Khidr L, Guo XE, Kim W, Lee YM, Krasieva T and Chen PL: A novel role of the chromokinesin Kif4A in DNA damage response. Cell Cycle. 7:2013–2020. 2008. View Article : Google Scholar : PubMed/NCBI

7 

Martinez NW, Xue X, Berro RG, Kreitzer G and Resh MD: Kinesin KIF4 regulates intracellular trafficking and stability of the human immunodeficiency virus type 1 Gag polyprotein. J Virol. 82:9937–9950. 2008. View Article : Google Scholar : PubMed/NCBI

8 

Bernasconi P, Cappelletti C, Navone F, Nessi V, Baggi F, Vernos I, Romaggi S, Confalonieri P, Mora M, Morandi L, et al: The kinesin superfamily motor protein KIF4 is associated with immune cell activation in idiopathic inflammatory myopathies. J Neuropathol Exp Neurol. 67:624–632. 2008. View Article : Google Scholar : PubMed/NCBI

9 

Midorikawa R, Takei Y and Hirokawa N: KIF4 motor regulates activity-dependent neuronal survival by suppressing PARP-1 enzymatic activity. Cell. 125:371–383. 2006. View Article : Google Scholar : PubMed/NCBI

10 

Mazumdar M, Lee JH, Sengupta K, Ried T, Rane S and Misteli T: Tumor formation via loss of a molecular motor protein. Curr Biol. 16:1559–1564. 2006. View Article : Google Scholar : PubMed/NCBI

11 

Carmeliet P: Angiogenesis in life, disease and medicine. Nature. 438:932–936. 2005. View Article : Google Scholar : PubMed/NCBI

12 

Olsson AK, Dimberg A, Kreuger J and Claesson-Welsh L: VEGF receptor signalling - in control of vascular function. Nat Rev Mol Cell Biol. 7:359–371. 2006. View Article : Google Scholar : PubMed/NCBI

13 

Cao Y: Positive and negative modulation of angiogenesis by VEGFR1 ligands. Sci Signal. 2:re12009. View Article : Google Scholar : PubMed/NCBI

14 

Ahmad S and Ahmed A: Elevated placental soluble vascular endothelial growth factor receptor-1 inhibits angiogenesis in preeclampsia. Circ Res. 95:884–891. 2004. View Article : Google Scholar : PubMed/NCBI

15 

Wu FT, Stefanini MO, Mac Gabhann F, Kontos CD, Annex BH and Popel AS: A systems biology perspective on sVEGFR1: its biological function, pathogenic role and therapeutic use. J Cell Mol Med. 14:528–552. 2010.

16 

Geissmann F, Manz MG, Jung S, Sieweke MH, Merad M and Ley K: Development of monocytes, macrophages, and dendritic cells. Science. 327:656–661. 2010. View Article : Google Scholar : PubMed/NCBI

17 

Clauss M, Weich H, Breier G, Knies U, Röckl W, Waltenberger J and Risau W: The vascular endothelial growth factor receptor Flt-1 mediates biological activities. Implications for a functional role of placenta growth factor in monocyte activation and chemotaxis. J Biol Chem. 271:17629–17634. 1996. View Article : Google Scholar : PubMed/NCBI

18 

Sawano A, Iwai S, Sakurai Y, Ito M, Shitara K, Nakahata T and Shibuya M: Flt-1, vascular endothelial growth factor receptor 1, is a novel cell surface marker for the lineage of monocyte-macrophages in humans. Blood. 97:785–791. 2001. View Article : Google Scholar : PubMed/NCBI

19 

Crowther M, Brown NJ, Bishop ET and Lewis CE: Micro-environmental influence on macrophage regulation of angiogenesis in wounds and malignant tumors. J Leukoc Biol. 70:478–490. 2001.PubMed/NCBI

20 

Hiratsuka S, Minowa O, Kuno J, Noda T and Shibuya M: Flt-1 lacking the tyrosine kinase domain is sufficient for normal development and angiogenesis in mice. Proc Natl Acad Sci USA. 95:9349–9354. 1998. View Article : Google Scholar : PubMed/NCBI

21 

Lewis CE and Pollard JW: Distinct role of macrophages in different tumor microenvironments. Cancer Res. 66:605–612. 2006. View Article : Google Scholar : PubMed/NCBI

22 

Kerber M, Reiss Y, Wickersheim A, Jugold M, Kiessling F, Heil M, Tchaikovski V, Waltenberger J, Shibuya M, Plate KH, et al: Flt-1 signaling in macrophages promotes glioma growth in vivo. Cancer Res. 68:7342–7351. 2008. View Article : Google Scholar : PubMed/NCBI

23 

Peppicelli S, Bianchini F and Calorini L: Inflammatory cytokines induce vascular endothelial growth factor-C expression in melanoma-associated macrophages and stimulate melanoma lymph node metastasis. Oncol Lett. 8:1133–1138. 2014.PubMed/NCBI

24 

Murakami M, Iwai S, Hiratsuka S, Yamauchi M, Nakamura K, Iwakura Y and Shibuya M: Signaling of vascular endothelial growth factor receptor-1 tyrosine kinase promotes rheumatoid arthritis through activation of monocytes/macrophages. Blood. 108:1849–1856. 2006. View Article : Google Scholar : PubMed/NCBI

25 

Murakami M, Zheng Y, Hirashima M, Suda T, Morita Y, Ooehara J, Ema H, Fong GH and Shibuya M: VEGFR1 tyrosine kinase signaling promotes lymphangiogenesis as well as angiogenesis indirectly via macrophage recruitment. Arterioscler Thromb Vasc Biol. 28:658–664. 2008. View Article : Google Scholar : PubMed/NCBI

26 

Matsui M, Takeda Y, Uemura S, Matsumoto T, Seno A, Onoue K, Tsushima H, Morimoto K, Soeda T, Okayama S, et al: Suppressed soluble Fms-like tyrosine kinase-1 production aggravates atherosclerosis in chronic kidney disease. Kidney Int. 85:393–403. 2014. View Article : Google Scholar

27 

Yamada KH, Nakajima Y, Geyer M, Wary KK, Ushio-Fukai M, Komarova Y and Malik AB: KIF13B regulates angiogenesis through Golgi to plasma membrane trafficking of VEGFR2. J Cell Sci. 127:4518–4530. 2014. View Article : Google Scholar : PubMed/NCBI

28 

Exertier P, Javerzat S, Wang B, Franco M, Herbert J, Platonova N, Winandy M, Pujol N, Nivelles O, Ormenese S, et al: Impaired angiogenesis and tumor development by inhibition of the mitotic kinesin Eg5. Oncotarget. 4:2302–2316. 2013. View Article : Google Scholar : PubMed/NCBI

29 

Cantley LC: The phosphoinositide 3-kinase pathway. Science. 296:1655–1657. 2002. View Article : Google Scholar : PubMed/NCBI

30 

Hemmings BA and Restuccia DF: The PI3K-PKB/Akt pathway. Cold Spring Harb Perspect Biol. 7:1–3. 2015. View Article : Google Scholar

31 

Park JK, Jeong JW, Kang MY, Baek JC, Shin JK, Lee SA, Choi WS, Lee JH and Paik WY: Inhibition of the PI3K-Akt pathway suppresses sFlt1 expression in human placental hypoxia models in vitro. Placenta. 31:621–629. 2010. View Article : Google Scholar : PubMed/NCBI

32 

Eubank TD, Roberts R, Galloway M, Wang Y, Cohn DE and Marsh CB: GM-CSF induces expression of soluble VEGF receptor-1 from human monocytes and inhibits angiogenesis in mice. Immunity. 21:831–842. 2004. View Article : Google Scholar : PubMed/NCBI

33 

Justiniano SE, Elavazhagan S, Fatehchand K, Shah P, Mehta P, Roda JM, Mo X, Cheney C, Hertlein E, Eubank TD, et al: Fcγ receptor-induced soluble vascular endothelial growth factor receptor-1 (VEGFR-1) production inhibits angiogenesis and enhances efficacy of anti-tumor antibodies. J Biol Chem. 288:26800–26809. 2013. View Article : Google Scholar : PubMed/NCBI

34 

Michell BJ, Griffiths JE, Mitchelhill KI, Rodriguez-Crespo I, Tiganis T, Bozinovski S, de Montellano PR, Kemp BE and Pearson RB: The Akt kinase signals directly to endothelial nitric oxide synthase. Curr Biol. 9:845–848. 1999. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Xu Y, Luan Y, Liu S, Sun J, Wang K, Cai J, Jiang W, Yang P, Wei F, Qu X, Qu X, et al: Kif4 regulates the expression of VEGFR1 through the PI3K/Akt signaling pathway in RAW264.7 monocytes/macrophages. Int J Mol Med 39: 1285-1290, 2017.
APA
Xu, Y., Luan, Y., Liu, S., Sun, J., Wang, K., Cai, J. ... Qu, X. (2017). Kif4 regulates the expression of VEGFR1 through the PI3K/Akt signaling pathway in RAW264.7 monocytes/macrophages. International Journal of Molecular Medicine, 39, 1285-1290. https://doi.org/10.3892/ijmm.2017.2936
MLA
Xu, Y., Luan, Y., Liu, S., Sun, J., Wang, K., Cai, J., Jiang, W., Yang, P., Wei, F., Qu, X."Kif4 regulates the expression of VEGFR1 through the PI3K/Akt signaling pathway in RAW264.7 monocytes/macrophages". International Journal of Molecular Medicine 39.5 (2017): 1285-1290.
Chicago
Xu, Y., Luan, Y., Liu, S., Sun, J., Wang, K., Cai, J., Jiang, W., Yang, P., Wei, F., Qu, X."Kif4 regulates the expression of VEGFR1 through the PI3K/Akt signaling pathway in RAW264.7 monocytes/macrophages". International Journal of Molecular Medicine 39, no. 5 (2017): 1285-1290. https://doi.org/10.3892/ijmm.2017.2936
Copy and paste a formatted citation
x
Spandidos Publications style
Xu Y, Luan Y, Liu S, Sun J, Wang K, Cai J, Jiang W, Yang P, Wei F, Qu X, Qu X, et al: Kif4 regulates the expression of VEGFR1 through the PI3K/Akt signaling pathway in RAW264.7 monocytes/macrophages. Int J Mol Med 39: 1285-1290, 2017.
APA
Xu, Y., Luan, Y., Liu, S., Sun, J., Wang, K., Cai, J. ... Qu, X. (2017). Kif4 regulates the expression of VEGFR1 through the PI3K/Akt signaling pathway in RAW264.7 monocytes/macrophages. International Journal of Molecular Medicine, 39, 1285-1290. https://doi.org/10.3892/ijmm.2017.2936
MLA
Xu, Y., Luan, Y., Liu, S., Sun, J., Wang, K., Cai, J., Jiang, W., Yang, P., Wei, F., Qu, X."Kif4 regulates the expression of VEGFR1 through the PI3K/Akt signaling pathway in RAW264.7 monocytes/macrophages". International Journal of Molecular Medicine 39.5 (2017): 1285-1290.
Chicago
Xu, Y., Luan, Y., Liu, S., Sun, J., Wang, K., Cai, J., Jiang, W., Yang, P., Wei, F., Qu, X."Kif4 regulates the expression of VEGFR1 through the PI3K/Akt signaling pathway in RAW264.7 monocytes/macrophages". International Journal of Molecular Medicine 39, no. 5 (2017): 1285-1290. https://doi.org/10.3892/ijmm.2017.2936
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