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