Skip to main content

Advertisement

SpringerLink
Log in

EGF Enhances ADSCs Secretion via ERK and JNK Pathways

  • Translational Biomedical Research
  • Published:
Cell Biochemistry and Biophysics Aims and scope Submit manuscript

Abstract

The objective of this work was to study the effect of epidermal growth factor (EGF) induced secretions of angiogenesis factors in adipose-derived stem cells (ADSCs) and the involvement of mitogen-activated protein kinases (MAPK). ADSCs were cultured and ELISA assays were performed to quantify the vascular endothelial growth factor, the hepatocyte growth factor, and the stromal derived factor-1 in ADSC-conditioned medium before and after EGF treatments and after pharmacological inhibition of MAPKs with PD98059, SB203580, and SP600125. The tube formation assay was used to test the effects of EGF treated and inhibitor treated ADSCs on the human umbilical vein endothelial cells (HUVECs) tube formation. Liposuction was applied and ADSCs were cultured successfully. The ADSCs released a variety of angiogenic factors, with the EGF treatments enhancing secretions and promoting the HUVEC tube formation. The MAPK inhibitors PD98059 and SP600125 increased the paracrine to promote tubular formation, while the SB203580 played an opposite role. In conclusion, (1) the in vitro cultured ADSCs secrete various angiogenic factors and the EGF amplifies the secretion and can enhance the ADSCs on the HUVEC tube formation. (2) ERK1/2 and JNK pathway may be involved in the enhanced secretion capacity of ADSCs while the p38 pathway may exert an opposite effect.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Zandonella, C. (2003). Tissue engineering: The beat goes on. Nature, 421, 884–886.

    Article  CAS  PubMed  Google Scholar 

  2. Polykandriotis, E., Arkudas, A., Horch, R. E., Stürzl, M., & Kneser, U. (2007). Autonomously vascularized cellular constructs in tissue engineering: opening a new perspective for biomedical science. Journal of Cellular and Molecular Medicine, 11, 6–20.

    Article  CAS  PubMed  Google Scholar 

  3. Zhu, Y., Liu, T., Song, K., Fan, X., Ma, X., & Cui, Z. (2008). Adipose-derived stem cell: A better stem cell than BMSC. Cell Research, 26, 664–675.

    CAS  Google Scholar 

  4. Fraser, J. K., Schreiber, R., Strem, B., Zhu, M., Alfonso, Z., Wulur, I., et al. (2006). Plasticity of human adipose stem cells toward endothelial cells and cardiomyocytes. Nature Clinical Practice Cardiovascular Medicine, 3S, 33–37.

    Article  Google Scholar 

  5. Nishimatsu, H., Suzuki, E., Kumano, S., Nomiya, A., Liu, M., Kume, H., et al. (2012). Adrenomedullin mediates adipose tissue-derived stem cell-induced restoration of erectile function in diabetic rats. Journal of Sexual Medicine, 9, 482–493.

    Article  CAS  PubMed  Google Scholar 

  6. Shoji, T., Ii, M., Mifune, Y., Matsumoto, T., Kawamoto, A., Kwon, S. M., et al. (2010). Local transplantation of human multipotent adipose-derived stem cells accelerates fracture healing via enhanced osteogenesis and angiogenesis. Laboratory Investigation, 90, 637–649.

    Article  PubMed  Google Scholar 

  7. Zhu, Y., Liu, T., Song, K., Jiang, B., Ma, X., & Cui, Z. (2009). Collagen–chitosan polymer as a scaffold for the proliferation of human adipose tissue-derived stem cells. Journal of Materials Science Materials in Medicine, 20, 799–808.

    Article  CAS  PubMed  Google Scholar 

  8. Tamama, K., Kawasaki, H., & Wells, A. (2010). Epidermal growth factor (EGF) treatment on multipotential stromal cells (MSCs). Possible enhancement of therapeutic potential of MSC. Journal of Biomedicine and Biotechnology, 2010, 795385.

    Article  PubMed Central  PubMed  Google Scholar 

  9. Zuk, P. A., Zhu, M., Mizuno, H., Huang, J., Futrell, J. W., Katz, A. J., et al. (2001). Multilinage cells from human adipose tissue: Implications for cell based therapies. Tissue Engineering, 7, 211–228.

    Article  CAS  PubMed  Google Scholar 

  10. Liu, S., Zhang, H., Zhang, X., Lu, W., Huang, X., Xie, H., et al. (2011). Synergistic angiogenesis promoting effects of extracellular matrix scaffolds and adipose-derived stem cells during wound repair. Tissue Engineering Part A, 17, 725–739.

    Article  CAS  PubMed  Google Scholar 

  11. Nie, C., Yang, D., Xu, J., Si, Z., Jin, X., & Zhang, J. (2011). Locally administered adipose-derived stem cells accelerate wound healing through differentiation and vasculogenesis. Cell Transplantation, 20, 205–216.

    Article  PubMed  Google Scholar 

  12. Colazzo, F., Chester, A. H., Taylor, P. M., & Yacoub, M. H. (2010). Induction of mesenchymal to endothelial transformation of adipose-derived stem cells. Journal of Heart Valve Disease, 19, 736–744.

    PubMed  Google Scholar 

  13. Kondo, K., Shintani, S., Shibata, R., Murakami, H., Murakami, R., Imaizumi, M., et al. (2009). Implantation of adipose derived regenerative cells enhances ischemia induced angiogenesis. Arteriosclerosis, Thrombosis, and Vascular Biology, 29, 61–66.

    Article  CAS  PubMed  Google Scholar 

  14. Cai, L., Johnstone, B. H., Cook, T. G., Tan, J., Fishbein, M. C., Chen, P. S., et al. (2009). IFATS collection: Human adipose tissue-derived stem cells induce angiogenesis and nerve sprouting following myocardial infarction, in conjunction with potent preservation of cardiac function. Stem Cells, 27, 230–237.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. Ferrara, N., Gerber, H. P., & LeCouter, J. (2003). The biology of VEGF and its receptors. Nature Medicine, 9, 669–676.

    Article  CAS  PubMed  Google Scholar 

  16. Saiki, A., Watanabe, F., Murano, T., Miyashita, Y., & Shirai, K. (2006). Hepatocyte growth factor secreted by cultured adipocytes promotes tube formation of vascular endothelial cells in vitro. International Journal of Obesity (London), 30, 1676–1684.

    Article  CAS  Google Scholar 

  17. Rosová, I., Dao, M., Capoccia, B., Link, D., & Nolta, J. A. (2008). Hypoxic preconditioning results in increased motility and improved therapeutic potential of human mesenchymal stem cells. Stem Cells, 26, 2173–2182.

    Article  PubMed Central  PubMed  Google Scholar 

  18. Nakao, N., Nakayama, T., Yahata, T., Muguruma, Y., Saito, S., Miyata, Y., et al. (2010). Adipose tissue-derived mesenchymal stem cells facilitate hematopoiesis in vitro and in vivo: advantages over bone marrow-derived mesenchymal stem cells. American Journal of Pathology, 177, 547–554.

    Article  PubMed Central  PubMed  Google Scholar 

  19. Crisostomo, P. R., Wang, Y., Markel, T. A., Wang, M., Lahm, T., & Meldrum, D. R. (2008). Human mesenchymal stem cells stimulated by TNF-α, LPS, or hypoxia produce growth factors by an NFκB- but not JNK-dependent mechanism. American Journal of Physiology, 294, C675–C682.

    Article  CAS  PubMed  Google Scholar 

  20. Wang, Y., Crisostomo, P. R., Wang, M., Markel, T. A., Novotny, N. M., & Meldrum, D. R. (2008). TGF-alpha increases human mesenchymal stem cell-secreted VEGF by MEK- and PI3-K- but not JNK- or ERK-dependent mechanisms. American Journal of Physiology, 295, R1115–R1123.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  21. Wang, Y., Wang, M., Abarbanell, A. M., Weil, B. R., Herrmann, J. L., Tan, J., et al. (2009). MEK mediates the novel cross talk between TNFR2 and TGF-EGFR in enhancing vascular endothelial growth factor (VEGF) secretion from human mesenchymal stem cells. Surgery, 146, 198–205.

    Article  PubMed  Google Scholar 

  22. Kajanne, R., Leppä, S., Luukkainen, P., Ustinov, J., Thiel, A., Ristimäki, A., et al. (2007). Hydrocortisone and indomethacin negatively modulate EGF-R signaling in human fetal intestine. Pediatric Research, 62, 570–575.

    Article  CAS  PubMed  Google Scholar 

  23. Long, J. L., Zuk, P., Berke, G. S., & Chhetri, D. K. (2010). Epithelial differentiation of adipose-derived stem cells for laryngeal tissue engineering. Laryngoscope, 120, 125–131.

    Article  CAS  PubMed  Google Scholar 

  24. Zavan, B., Michelotto, L., Lancerotto, L., Della Puppa, A., D’Avella, D., Abatangelo, G., et al. (2010). Neural potential of a stem cell population in the adipose and cutaneous tissues. Neurological Research, 32, 47–54.

    Article  PubMed  Google Scholar 

  25. Chang, J. C., Lee, P. C., Lin, Y. C., Lee, K. W., & Hsu, S. H. (2011). Primary adipose-derived stem cells enriched by growth factor treatment improves cell adaptability toward cardiovascular differentiation in a rodent model of acute myocardial infarction. Stem Cells, 6, 21–37.

    Google Scholar 

  26. Wetzker, R., & Böhmer, F. D. (2003). Transactivation joins multiple tracks to the ERK/MAPK cascade. Nature Reviews Molecular Cell Biology, 4, 651–657.

    Article  CAS  PubMed  Google Scholar 

  27. Gan, Y., Shi, C., Inge, L., Hibner, M., Balducci, J., & Huang, Y. (2010). Differential roles of ERK and Akt pathways in regulation of EGFR-mediated signaling and motility in prostate cancer cells. Oncogene, 29, 4947–4958.

    Article  CAS  PubMed  Google Scholar 

  28. Plotnikov, A., Zehorai, E., Procaccia, S., & Seger, R. (2010). The MAPK cascades: Signaling components, nuclear roles and mechanisms of nuclear translocation. Biochimica et Biophysica Acta, 1813, 1619–1633.

    Article  PubMed  Google Scholar 

  29. Nakamura, S., Chikaraishi, Y., Tsuruma, K., Shimazawa, M., & Hara, H. (2010). Ruboxistaurin, a PKCbeta inhibitor, inhibits retinal neovascularization via suppression of phosphorylation of ERK1/2 and Akt. Experimental Eye Research, 90, 137–145.

    Article  CAS  PubMed  Google Scholar 

  30. Pang, X., Yi, T., Yi, Z., Cho, S. G., Qu, W., Pinkaew, D., et al. (2009). Morelloflavone, a biflavonoid, inhibits tumor angiogenesis by targeting rho GTPases and extracellular signal-regulated kinase signaling pathways. Cancer Research, 69, 518–525.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. Sabri, A., Ziaee, A. A., Ostad, S. N., Alimoghadam, K., & Ghahremani, M. H. (2011). Crosstalk of EGF-directed MAPK signalling pathways and its potential role on EGF-induced cell proliferation and COX-2 expression in human mesenchymal stem cells. Cell Biochemistry and Function, 29, 64–70.

    Article  CAS  PubMed  Google Scholar 

  32. Miura, S., Matsuo, Y., & Saku, K. (2008). Jun N-terminal kinase inhibitor blocks angiogenesis by blocking VEGF secretion and an MMP pathway. Journal of Atherosclerosis and Thrombosis, 15, 69–74.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Plastic Surgery Department, Xuzhou Medical College Affiliated Hospital, 99 Huaihai Road West, Xuzhou, 221002, Jiangsu, China

    Qiang Li, Ai-jun Zhang, Chang-bo Tao, Xue-yang Li & Pei-sheng Jin

  2. Department of Otolaryngology, Xuzhou Medical College Affiliated Hospital, Xuzhou, Jiangsu, China

    Pei-hua Li

  3. Face and Neck Plastic Surgery Center of Plastic Surgery Hospital, Chinese Academy of Medical Sciences, Beijing, China

    Dian-ju Hou

Authors
  1. Qiang Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Pei-hua Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Dian-ju Hou
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ai-jun Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Chang-bo Tao
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Xue-yang Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Pei-sheng Jin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Pei-sheng Jin.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Li, Q., Li, Ph., Hou, Dj. et al. EGF Enhances ADSCs Secretion via ERK and JNK Pathways. Cell Biochem Biophys 69, 189–196 (2014). https://doi.org/10.1007/s12013-013-9769-3

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12013-013-9769-3

Keywords

Search

Navigation