title: SDF-1α-induced dual pairs of E-selectin/ligand mediate endothelial progenitor cell homing to critical ischemia.
abstract: Homing of endothelial progenitor cells (EPC) to the ischemic tissues is a key event in neovascularization and tissue regeneration. In response to ischemic insult, injured tissues secrete several chemo-cytokines, including stromal cell-derived factor-1α (SDF-1α), which triggers mobilization and homing of bone marrow-derived EPC (BMD-EPC). We previously reported that SDF-1α-induced EPC homing is mediated by a panel of adhesion molecules highly or selectively expressed on the activated endothelium in ischemic tissues, including E-selectin. Elevated E-selectin on wound vasculature serve as docking sites for circulating EPC, which express counterpart E-selectin ligands. Here, we show that SDF-1α presented in wound tissue and released into circulation can act both locally and remotely to induce ischemic tissue endothelium and BMD-EPC to express both E-selectin and its ligands. By performing BM transplantation using E-selectin-/-and E-selectin+/+mice as the donors and recipients respectively, we demonstrate that upregulated dual E-selectin/ligand pairs reciprocally expressed on ischemic tissue endothelium and BMD-EPC act as double-locks to secure targeted EPC- endothelium interactions by which to facilitate EPC homing and promote neovascularization and tissue repair. These findings describe a novel mechanism for BMD-EPC homing and indicate that dual E-selectin/ligand pairs may be effective targets/tools for therapeutic neovascularization and targeted cell delivery.
authors.affiliation: Department of Surgery, University of Miami School of Medicine, Miami, 33136, USA.
authors.forename: Zhao-Jun
authors.initials: ZJ
authors.lastname: Liu
authors.affiliation: Department of Surgery, University of Miami School of Medicine, Miami, 33136, USA.
authors.forename: Runxia
authors.initials: R
authors.lastname: Tian
authors.affiliation: Department of Surgery, University of Miami School of Medicine, Miami, 33136, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Surgery, University of Miami School of Medicine, Miami, 33136, USA.|Yantai University, School of Pharmacy, Shandong 264005, China.
authors.forename: Leiming
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Surgery, University of Miami School of Medicine, Miami, 33136, USA.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Shao
authors.affiliation: Department of Surgery, University of Miami School of Medicine, Miami, 33136, USA.|Department of Molecular Biology Laboratory, Shanghai Sixth People's Hospital, Shanghai Jiaotong University, Shanghai, 200233, China.
authors.forename: Cuixia
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of Surgery, University of Miami School of Medicine, Miami, 33136, USA.
authors.forename: Omaida C
authors.initials: OC
authors.lastname: Velazquez
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D002465:Cell Movement; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000008:administration & dosage / Q000378:metabolism*; D019040:E-Selectin / Q000235:genetics / Q000378:metabolism*; D066026:Endothelial Progenitor Cells / Q000378:metabolism*; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D007511:Ischemia / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009389:Neovascularization, Pathologic; D017468:Receptors, Fibroblast Growth Factor; D012795:Sialoglycoproteins; D014945:Wound Healing
chemical_list: C497483:CD44 protein, human; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse; D019040:E-Selectin; D018960:Hyaluronan Receptors; D017468:Receptors, Fibroblast Growth Factor; D012795:Sialoglycoproteins; C086711:cysteine-rich fibroblast growth factor receptor