Skip to main content
SpringerLink
Log in

The role of SDF-1α/Rac pathway in the regulation of endothelial progenitor cell polarity; homing and expression of Rac1, Rac2 during endothelial repair

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

The Stromal cell-derived factor-1 (SDF-1)/CXC chemokine receptor 4 (CXCR4) system is considered to be of great importance in diseases involving cardiogenesis and angiogenesis. The SDF-1α-RAC signaling pathway plays a pivotal role in a cell’s polarity and serves to activate cell morphology variation and to control the direction of migration. We aimed to study whether the polarity of endothelial progenitor cells (EPCs) is changed by the induction of the SDF-1α-RAC signaling pathway, to investigate the mechanism of the effect of polarity on the homing action of EPCs, and to explore the gene and protein expression of Rac1/2 during endothelial repair. We measured the EPC characteristics of polarity induced by various final concentrations of SDF-1α; our observations included morphology variation, migration direction, and excursion. Of the dynamic variation and cytoskeleton rearrangement of EPCs induced by different final concentrations of SDF-1α, the most obvious variation was exhibited at the SDF-1α concentration of 200 ng/ml. Obvious polarity variations were also found in the EPCs and signal receptors induced by the SDF-1α concentration of 200 ng/ml. The Western blot analysis of Rac1 and Rac2 showed that the addition of AMD 3100 significantly inhibited the expression of Rac. The SDF-1α pathway potentially regulates the expression of Rac1/2. The actual excursion vector and the direction of the migration of EPCs induced by SDF-1α follows polarity, thus indicating the importance of further exploration regarding the homing induction of EPCs.

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
Fig. 6

Similar content being viewed by others

References

  1. Sbaa E, Dewever J, Martinive P, Bouzin C, Frérart F, Balligand JL, Dessy C, Feron O (2006) Caveolin plays a central role in endothelial progenitor cell mobilization and homing in SDF-1-driven postischemic vasculogenesis. Circ Res 98:1219–1227

    Article  PubMed  CAS  Google Scholar 

  2. De La Luz Sierra M, Yang F, Narazaki M, Salvucci O, Davis D, Yarchoan R, Zhang HH, Fales H, Tosato G (2004) Differential processing of stromal-derived factor-1alpha and stromal-derived factor-1beta explains functional diversity. Blood 103:2452–2459

    Article  Google Scholar 

  3. Janowski M (2009) Functional diversity of SDF-1 splicing variants. Cell Adh Migr 3:243–249

    Article  PubMed  Google Scholar 

  4. Nagasawa T, Hirota S, Tachibana K, Takakura N, Nishikawa S, Kitamura Y, Yoshida N, Kikutani H, Kishimoto T (1996) Defects of B-cell lymphopoiesis and bone-marrow myelopoiesis in mice lacking the CXC chemokine PBSF/SDF-1. Nature 382:635–638

    Article  PubMed  CAS  Google Scholar 

  5. Abbott JD, Huang Y, Liu D, Hickey R, Krause DS, Giordano FJ (2004) Stromal cell-derived factor-1alpha plays a critical role in stem cell recruitment to the heart after myocardial infarction but is not sufficient to induce homing in the absence of injury. Circulation 110:3300–3305

    Article  PubMed  Google Scholar 

  6. Wei YJ, Tang Y, Li J, Cui CJ, Zhang H, Zhang XL, Zhang H, Hu SS (2007) Cloning and expression pattern of dog SDF-1 and the implications of altered expression of SDF-1 in ischemic myocardium. Cytokine 40:52–59

    Article  PubMed  CAS  Google Scholar 

  7. Proulx C, El-Helou V, Gosselin H, Clement R, Gillis MA, Villeneuve L, Calderone A (2007) Antagonism of stromal cell-derived factor-1alpha reduces infarct size and improves ventricular function after myocardial infarction. Pflugers Arch 455:241–250

    Article  PubMed  CAS  Google Scholar 

  8. Chang LT, Yuen CM, Sun CK, Wu CJ, Sheu JJ, Chua S, Yeh KH, Yang CH, Youssef AA, Yip HK (2009) Role of stromal cell-derived factor-1alpha, level and value of circulating interleukin-10 and endothelial progenitor cells in patients with acute myocardial infarction undergoing primary coronary angioplasty. Circ J 73:1097–1104

    Article  PubMed  CAS  Google Scholar 

  9. Asahara T, Murohara T, Sullivan A, Silver M, van der Zee R, Li T, Witzenbichler B, Schatteman G, Isner JM (1997) Isolation of putative progenitor endothelial cells for angiogenesis. Science 275:964–967

    Article  PubMed  CAS  Google Scholar 

  10. Jia L, Takahashi M, Yoshioka T, Morimoto H, Ise H, Ikeda U (2006) Therapeutic potential of endothelial progenitor cells for cardiovascular diseases. Curr Vasc Pharmacol 4:59–65

    Article  PubMed  CAS  Google Scholar 

  11. Hu X, Dai S, Wu WJ, Tan W, Zhu X, Mu J, Guo Y, Bolli R, Rokosh G (2007) Stromal cell derived factor-1 alpha confers protection against myocardial ischemia/reperfusion injury: role of the cardiac stromal cell derived factor-1 alpha CXCR4 axis. Circulation 116:654–663

    Article  PubMed  CAS  Google Scholar 

  12. Chade AR, Zhu XY, Krier JD, Jordan KL, Textor SC, Grande JP, Lerman A, Lerman LO (2010) Endothelial progenitor cells homing and renal repair in experimental renovascular disease. Stem Cells 28:1039–1047

    Article  PubMed  CAS  Google Scholar 

  13. Jin H, Aiyer A, Su J, Borgstrom P, Stupack D, Friedlander M, Varner J (2006) A homing mechanism for bone marrow-derived progenitor cell recruitment to the neovasculature. J Clin Invest 116:652–662

    Article  PubMed  CAS  Google Scholar 

  14. Huttenlocher A (2005) Cell polarization mechanisms during directed cell migration. Nat Cell Bio 7:336–337

    Article  CAS  Google Scholar 

  15. Nishiya N, Kiosses WB, Han J, Ginsberg MH (2005) An alpha4 integrin-paxillin-Arf-GAP complex restricts Rac activation to the leading edge of migrating cells. Nat Cell Biol 7:343–352

    Article  PubMed  CAS  Google Scholar 

  16. Pearce G, Angeli V, Randolph GJ, Junt T, von Andrian U, Schnittler HJ, Jessberger R (2006) Signaling protein SWAP-70 is required for efficient B cell homing to lymphoid organs. Nat Immunol 7:827–834

    Article  PubMed  CAS  Google Scholar 

  17. Asahara T, Takahashi T, Masuda H, Kalka C, Chen D, Iwaguro H, Inai Y, Silver M, Isner JM (1999) VEGF contributes to postnatal neovascularization by mobilizing bone marrow-derived endothelial progenitor cells. EMBO J 18:3964–3972

    Article  PubMed  CAS  Google Scholar 

  18. Fedyk ER, Jones D, Critchley HO, Phipps RP, Blieden TM, Springer TA (2001) Expression of stromal-derived factor-1 is decreased by IL-1 and TNF and in dermal wound healing. J Immunol 166:5749–5754

    PubMed  CAS  Google Scholar 

  19. Ceradini DJ, Kulkarni AR, Callaghan MJ, Tepper OM, Bastidas N, Kleinman ME, Capla JM, Galiano RD, Levine JP, Gurtner GC (2004) Progenitor cell trafficking is regulated by hypoxic gradients through HIF-1 induction of SDF-1. Nat Med 10:858–864

    Article  PubMed  CAS  Google Scholar 

  20. Urbich C, Dimmeler S (2004) Endothelial progenitor cells: characterization and role in vascular biology. Circ Res 95:343–353

    Article  PubMed  CAS  Google Scholar 

  21. Peled A, Kollet O, Ponomaryov T, Petit I, Franitza S, Grabovsky V, Slav MM, Nagler A, Lider O, Alon R, Zipori D, Lapidot T (2000) The chemokine SDF-1 activates the integrins LFA-1, VLA-4, and VLA-5 on immature human CD34(+) cells: role in transendothelial/stromal migration and engraftment of NOD/SCID mice. Blood 95:3289–3296

    PubMed  CAS  Google Scholar 

  22. Servant G, Weiner OD, Herzmark P, Balla T, Sedat JW, Bourne HR (2000) Polarization of chemoattractant receptor signaling during neutrophil chemotaxis. Science 287:1037–1040

    Article  PubMed  CAS  Google Scholar 

  23. van Buul JD, Voermans C, van Gelderen J, Anthony EC, van der Schoot CE, Hordijk PL (2003) Leukocyte-Endothelium Interaction Promotes SDF-1-dependent Polarization of CXCR4. J Bio Chem 278:30302–30310

    Article  Google Scholar 

  24. Avigdor A, Goichberg P, Shivtiel S, Dar A, Peled A, Samira S, Kollet O, Hershkoviz R, Alon R, Hardan I, Ben-Hur H, Naor D, Nagler A, Lapidot T (2004) CD44 and hyaluronic acid cooperate with SDF-1 in the trafficking of human CD34 + stem/progenitor cells to bone marrow. Blood 103:2981–2989

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study was supported by Natural Science Foundation of China (30700318), National Basic Research Program of China (2011CB503905, 2010CB529505); National 863 High Technology Research and Development Program of China (2007AA02Z450) and “Shu Guang” Project of Shanghai (08SG03).

Author information

Authors and Affiliations

  1. Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, People’s Republic of China

    Li Shen, Yongxing Gao, Juying Qian, Yizhe Wu, Aijun Sun, Yunzeng Zou & Junbo Ge

  2. Key Laboratory of Molecular Medicine, Ministry of Education, Fudan University, Shanghai, 200032, People’s Republic of China

    Mingming Zhou

  3. Nantong University, 9 Seyuan Road, Nantong, 226019, People’s Republic of China

    Mingming Zhou

Authors
  1. Li Shen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yongxing Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Juying Qian
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yizhe Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mingming Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Aijun Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yunzeng Zou
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Junbo Ge
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Juying Qian or Junbo Ge.

Additional information

Li Shen and Yongxing Gao contributed equally to this study.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Shen, L., Gao, Y., Qian, J. et al. The role of SDF-1α/Rac pathway in the regulation of endothelial progenitor cell polarity; homing and expression of Rac1, Rac2 during endothelial repair. Mol Cell Biochem 365, 1–7 (2012). https://doi.org/10.1007/s11010-011-1083-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-011-1083-z

Keywords

Search

Navigation