A novel mechanism for endothelial progenitor cells homing: The SDF-1/CXCR4-Rac pathway may regulate endothelial progenitor cells homing through cellular polarization.
The term "homing" describes the migration of circulating stem/progenitor cells into a target tissue. Mobilization of endothelial progenitor cells (EPCs) and regulation of their homing to ischemic tissues has become a novel therapy for accelerating endothelial repair in ischemic heart disease. However, the mechanisms for EPCs' directional migration and homing remain uncertain. Migrating cells, including EPCs, are characterized by their cellular polarity and polarity change (polarization). Polarization is a critical first step for cellular direction modulation by which cells form the "directing edge" and move towards chemokines during cell mobilization. In the process, Rac proteins act a crucial regulation proteins, also named as "compass" protein, which play an essential role in manipulation intracellular signaling of cells responsible for migration and homing. It is also well established that stromal cell-derived factor-1 (SDF-1), mediates trafficking and homing of EPCs to injury microenvironment. We hypothesize that SDF-1 maybe directs EPCs homing through a novel pathway. In this way, SDF-1α changes EPCs' polarity through activating SDF-1/CXCR4 axis downstream Rac GTPases and thus regulates their migration and homing. By revealing the intrinsic relation of SDF-1α and Rac and underlying mechanism on EPCs' homing, a new target to regulate EPCs' homing can be found.
Shanghai Institute of Cardiovascular Disease, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai 200032, People's Republic of China.
Li
L
Shen
Yongxing
Y
Gao
Juying
J
Qian
Aijun
A
Sun
Junbo
J
Ge
D000818:Animals; D002465:Cell Movement; D054377:Chemokine CXCL12 / Q000378:metabolism*; D018925:Chemokines / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology*; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006801:Humans; D008954:Models, Biological; D008962:Models, Theoretical; D009206:Myocardium / Q000473:pathology; D019718:Receptors, CXCR4 / Q000378:metabolism*; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology*; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*
D054377:Chemokine CXCL12; D018925:Chemokines; C107953:RAC1 protein, human; D019718:Receptors, CXCR4; D020830:rac1 GTP-Binding Protein