Molecular and Cellular Biochemistry

, Volume 365, Issue 1–2, pp 1–7 | Cite as

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



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.


SDF-1α EPCs Cell polarity Rac1 Rac2 



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).


  1. 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 98:1219–1227PubMedCrossRefGoogle Scholar
  2. 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 103:2452–2459CrossRefGoogle Scholar
  3. 3.
    Janowski M (2009) Functional diversity of SDF-1 splicing variants. Cell Adh Migr 3:243–249PubMedCrossRefGoogle Scholar
  4. 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 382:635–638PubMedCrossRefGoogle Scholar
  5. 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 110:3300–3305PubMedCrossRefGoogle Scholar
  6. 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 40:52–59PubMedCrossRefGoogle Scholar
  7. 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 455:241–250PubMedCrossRefGoogle Scholar
  8. 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 73:1097–1104PubMedCrossRefGoogle Scholar
  9. 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 275:964–967PubMedCrossRefGoogle Scholar
  10. 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 4:59–65PubMedCrossRefGoogle Scholar
  11. 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 116:654–663PubMedCrossRefGoogle Scholar
  12. 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 28:1039–1047PubMedCrossRefGoogle Scholar
  13. 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 116:652–662PubMedCrossRefGoogle Scholar
  14. 14.
    Huttenlocher A (2005) Cell polarization mechanisms during directed cell migration. Nat Cell Bio 7:336–337CrossRefGoogle Scholar
  15. 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 7:343–352PubMedCrossRefGoogle Scholar
  16. 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 7:827–834PubMedCrossRefGoogle Scholar
  17. 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 18:3964–3972PubMedCrossRefGoogle Scholar
  18. 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 166:5749–5754PubMedGoogle Scholar
  19. 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 10:858–864PubMedCrossRefGoogle Scholar
  20. 20.
    Urbich C, Dimmeler S (2004) Endothelial progenitor cells: characterization and role in vascular biology. Circ Res 95:343–353PubMedCrossRefGoogle Scholar
  21. 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 95:3289–3296PubMedGoogle Scholar
  22. 22.
    Servant G, Weiner OD, Herzmark P, Balla T, Sedat JW, Bourne HR (2000) Polarization of chemoattractant receptor signaling during neutrophil chemotaxis. Science 287:1037–1040PubMedCrossRefGoogle Scholar
  23. 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 278:30302–30310CrossRefGoogle Scholar
  24. 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 103:2981–2989PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2011

Authors and Affiliations

  • Li Shen
    • 1
  • Yongxing Gao
    • 1
  • Juying Qian
    • 1
  • Yizhe Wu
    • 1
  • Mingming Zhou
    • 2
    • 3
  • Aijun Sun
    • 1
  • Yunzeng Zou
    • 1
  • Junbo Ge
    • 1
  1. 1.Shanghai Institute of Cardiovascular Diseases, Zhongshan HospitalFudan UniversityShanghaiPeople’s Republic of China
  2. 2.Key Laboratory of Molecular Medicine, Ministry of EducationFudan UniversityShanghaiPeople’s Republic of China
  3. 3.Nantong UniversityNantongPeople’s Republic of China

Personalised recommendations