| First Author | Lv Y | Year | 2020 |
| Journal | Exp Eye Res | Volume | 193 |
| Pages | 107991 | PubMed ID | 32142723 |
| Mgi Jnum | J:297773 | Mgi Id | MGI:6479251 |
| Doi | 10.1016/j.exer.2020.107991 | Citation | Lv Y, et al. (2020) Integrin alpha5beta1 promotes BMCs mobilization and differentiation to exacerbate choroidal neovascularization. Exp Eye Res 193:107991 |
| abstractText | Choroidal neovascularization (CNV) is an acknowledged pathogenic mechanism of various ocular diseases, and in situ cells and mobilized bone marrow-derived cells (BMCs) are thought to participate in this process. We aimed to evaluate the roles of integrin alpha5 in BMCs and vascular endothelial cells (VECs) in the CNV process mediated by SDF-1/CXCR4 signaling. Adult wild-type mice were engrafted with whole BMCs obtained from GFP transgenic mice and then laser injured to induce CNV. BMCs and RF/6A cells were cultured to discover the mechanism of CNV in vitro. BMCs were mobilized to CNV areas, which expressed elevated SDF-1 and CXCR4. When SDF-1 was intravitreally injected, the number of BMCs was profoundly increased. In the SDF-1-treated group, the levels of integrin alpha5 expressed on BMCs and VECs were significantly higher than those on the cells in the control group. SDF-1 significantly increased the expression and positive ratio of integrin alpha5, which was involved in the recruitment and differentiation of BMCs into BMC-derived VECs, and these effects were suppressed by the CXCR4 inhibitor AMD3100. The PI3K/AKT pathway rather than the ERK pathway mediated SDF-1/CXCR4 induction of integrin alpha5. Integrin alpha5 suppression efficiently prevented the production of TGF-beta and bFGF but not VEGF. Inhibiting the SDF-1/CXCR4-PI3K/AKT-integrin alpha5 axis reduced CNV severity. Integrin alpha5 participates in BMC recruitment and differentiation in SDF-1/CXCR4-induced CNV and inhibition of this pathway may be a new approach to inhibit CNV. |
