miR‐539‐5p inhibits experimental choroidal neovascularization by targeting CXCR7

Abstract

Stromal cell-derived factor-1 (SDF-1) has been previously confirmed to participate in the formation of choroidal neovascularization (CNV) via its receptor, CXC chemokine receptor (CXCR) 4; CXCR7 is a recently identified receptor for SDF-1. The molecular mechanisms and therapeutic value of CXCR7 in CNV remain undefined. In this study, experimental CNV was induced by laser photocoagulation in Brown-Norway pigmented rats, and aberrant CXCR7 overexpression was detected in the retinal pigment epithelial/choroid/sclera tissues of laser-injured eyes. Blockade of CXCR7 activation via CXCR7 knockdown or neutralizing Ab administration inhibited SDF-1-induced cell survival and the tubular formation of human retinal microvascular endothelial cells (HRMECs) in vitro and reduced CNV leakage and lesion size in vivo. By using microRNA array screening and bioinformatic analyses, we identified miR-539-5p as a regulator of CXCR7. Transfection of HRMECs and choroid-retinal endothelial (RF/6A) cells with the miR-539-5p mimic inhibited their survival and tube formation, whereas CXCR7 overexpression rescued the suppressive effect of miR-539-5p. The antiangiogenic activities of the miR-539-5p mimic were additionally demonstrated in vivo by intravitreal injection. ERK1/2 and AKT signaling downstream of CXCR7 is involved in the miR-539-5p regulation of endothelial cell behaviors. These findings suggest that the manipulation of miR-539-5p/CXCR7 levels may have important therapeutic implications in CNV-associated diseases.-Feng, Y., Wang, J., Yuan, Y., Zhang, X., Shen, M., Yuan, F. miR-539-5p inhibits experimental choroidal neovascularization by targeting CXCR7.

Chitinase-3-Like-1 Promotes M2 Macrophage Differentiation and Induces Choroidal Neovascularization in Neovascular Age-Related Macular Degeneration

“…24 Since an interesting study reported that RF/6A lost some key EC markers, 25 we compared its angiogenic reactions to VEGFA with human microvascular ECs (HMVECs) and got identical responsiveness. Finally, as RF/ 6A is the most prevalent in vitro choroidal and retinal EC model, 26,27 we decided to include it in our tube formation experiment. Firstly, RAW264.7 cell lines were cultured with recombinant CHI3L1 for 24 hours, and then we removed the CHI3L1-containing medium and collected the conditioned supernatant medium (CM) for another 24 hours.…”

MiR-539-5p alleviates sepsis-induced acute lung injury by targeting ROCK1

“…MiR-27a mediated the protective effect of paclitaxel in the damaged liver from septic mice by suppressing NF-kB/TAB3 signaling pathway [13]. MiR-539-5p has been shown as a potent regulator in choroidal neovascularization and the migration of mesenchymal stem cells in fracture healing [14,15]. However, whether it may exert beneficial effect in ALI remains unclear.…”

Altered Long Non-coding RNAs Involved in Immunological Regulation and Associated with Choroidal Neovascularization in Mice

“…Studies have shown that chemokine (C-X-C motif) ligand 8 (CXCL8) and monocyte chemoattractant protein-1 (MCP-1), and chemokine receptors such as CXC chemokine receptor 3 (CXCR3) have been reported to be involved in CNV and AMD pathogenesis [47,48]. A study showed that miR-539-5p attenuates experimental CNV through targeting CXC chemokine receptor 7 (CXCL7) [49], indicating that non-coding RNAs are involved in the functional effect of chemokines and their receptors that contribute to the formation of CNV. In the present study, GO and KEGG analyses showed that altered genes enriched in immune system process, immune response, chemokine signaling pathway and cytokine-cytokine receptor interaction, indicating that lncRNAs may regulate chemokines, cytokines and their receptors in the pathogenesis of CNV formation through their target genes.…”