Wayne State University
A Critical Role Of Cxcr2 Pdz Motif-Mediated Interactions In Endothelial Progenitor Cell Homing And Angiogenesis
Abstract
dc:description.abstract<p>Bone marrow-derived endothelial progenitor cells (EPCs) participate in postnatal vascularization in response to growth factors, cytokines, and chemokines. Chemokine receptor CXCR2 and its cognate ligands are reported to mediate EPC recruitment and angiogenesis. CXCR2 possesses a consensus PSD-95/DlgA/ZO-1 (PDZ) motif at its carboxyl terminus. The PDZ motif has been reported to regulate cellular signaling and functions. Here we investigated the potential role of the PDZ motif in CXCR2-mediated EPC motility and angiogenesis. We have found that introducing exogenous CXCR2 C-terminus significantly attenuated in vitro EPC migration and angiogenic activities in response to CXCR2 ligands, as well as in vivo EPC angiogenesis. Meanwhile, the activation of RhoA, p38, ERK1/2, and Akt has also been inhibited due to the exogenous CXCR2 C-terminus. On the other hand, delivering CXCR2 C-terminus without PDZ motif into EPCs did not significantly affect the functions of EPCs. Moreover, biochemistry study suggested that NHERF1, a PDZ domain containing scaffolding protein, preferred to interact with CXCR2 and its downstream effector, PLC-β3 in EPCs. Taken together, the data has demonstrated the role of CXCR2 PDZ motif-mediated macromolecular complex in EPC homing and angiogenesis and also indicated potentially involved signaling pathways. The findings suggested that targeting CXCR2 PDZ motif-mediated interactions in EPCs may be a novel therapeutic approach in EPC dependent angiogenesis related diseases.</p>
Degree
thesis:*- Name thesis:degree_name
- Ph.D.
- Level thesis:degree_level
- Open Access Dissertation
- Discipline thesis:degree_discipline
- Biochemistry and Molecular Biology
- Year dc:date.available
- 2016
Author and committee
dc:creator, dc:contributor.*- Author dc:creator
-
- Hou, Yuning
- Contributors dc:contributor
-
- Chunying Li
Subjects
dc:subject × 8Identifiers
dc:identifier.*- Repository record dc:identifier
- https://digitalcommons.wayne.edu/oa_dissertations/1448
- OAI identifier oai:identifier
- oai:digitalcommons.wayne.edu:oa_dissertations-2447