| First Author | Youn SW | Year | 2011 |
| Journal | Blood | Volume | 117 |
| Issue | 16 | Pages | 4376-86 |
| PubMed ID | 21200018 | Mgi Jnum | J:172617 |
| Mgi Id | MGI:5008365 | Doi | 10.1182/blood-2010-07-295964 |
| Citation | Youn SW, et al. (2011) COMP-Ang1 stimulates HIF-1alpha-mediated SDF-1 overexpression and recovers ischemic injury through BM-derived progenitor cell recruitment. Blood 117(16):4376-86 |
| abstractText | Recruitment and adhesion of bone marrow (BM)-derived circulating progenitor cells to ischemic tissue are important for vasculogenesis and tissue repair. Recently, we found cartilage oligomeric matrix protein (COMP)-Ang1 is a useful cell-priming agent to improve the therapeutic efficacy of progenitor cells. However, the effect and the underlying mechanisms of COMP-Ang1 on recruitment of BM-derived progenitor cells (BMPCs) to foci of vascular injury have not been well defined. Here, we found that COMP-Ang1 is a critical stimulator of stromal cell-derived factor 1 (SDF-1), the principal regulator of BM-cell trafficking. Furthermore, SDF-1 stimulation by COMP-Ang1 was blocked by small-interfering RNA (siRNA) against hypoxia-inducible factor-1alpha (HIF-1alpha). COMP-Ang1 increased the synthesis of HIF-1alpha by activating mammalian target of rapamycin (mTOR) in hypoxic endothelium. The intermediate mechanism transmitting the COMP-Ang1 signal to the downstream mTOR/HIF-1alpha/SDF-1 pathway was the enhanced binding of the Tie2 receptor with integrin-linked kinase (ILK), an upstream activator of mTOR. In the mouse ischemic model, local injection of COMP-Ang1 stimulated the incorporation of BMPCs into ischemic limb, thereby enhancing neovasculogenesis and limb salvage. Collectively, our findings identify the COMP-Ang1/HIF-1alpha/SDF-1 pathway as a novel inducer of BMPC recruitment and neovasculogenesis in ischemic disease. |
