| First Author | Sun Y | Year | 2017 |
| Journal | FASEB J | Volume | 31 |
| Issue | 10 | Pages | 4492-4502 |
| PubMed ID | 28646017 | Mgi Jnum | J:253392 |
| Mgi Id | MGI:6108854 | Doi | 10.1096/fj.201700172R |
| Citation | Sun Y, et al. (2017) RORalpha modulates semaphorin 3E transcription and neurovascular interaction in pathological retinal angiogenesis. FASEB J 31(10):4492-4502 |
| abstractText | Pathological proliferation of retinal blood vessels commonly causes vision impairment in proliferative retinopathies, including retinopathy of prematurity. Dysregulated crosstalk between the vasculature and retinal neurons is increasingly recognized as a major factor contributing to the pathogenesis of vascular diseases. Class 3 semaphorins (SEMA3s), a group of neuron-secreted axonal and vascular guidance factors, suppress pathological vascular growth in retinopathy. However, the upstream transcriptional regulators that mediate the function of SEMA3s in vascular growth are poorly understood. Here we showed that retinoic acid receptor-related orphan receptor alpha (RORalpha), a nuclear receptor and transcription factor, is a novel transcriptional regulator of SEMA3E-mediated neurovascular coupling in a mouse model of oxygen-induced proliferative retinopathy. We found that genetic deficiency of RORalpha substantially induced Sema3e expression in retinopathy. Both RORalpha and SEMA3E were expressed in retinal ganglion cells. RORalpha directly bound to a specific ROR response element on the promoter of Sema3e and negatively regulated Sema3e promoter-driven luciferase expression. Suppression of Sema3e using adeno-associated virus 2 carrying short hairpin RNA targeting Sema3e promoted disoriented pathological neovascularization and partially abolished the inhibitory vascular effects of RORalpha deficiency in retinopathy. Our findings suggest that RORalpha is a novel transcriptional regulator of SEMA3E-mediated neurovascular coupling in pathological retinal angiogenesis.-Sun, Y., Liu, C.-H., Wang, Z., Meng, S. S., Burnim, S. B., SanGiovanni, J. P., Kamenecka, T. M., Solt, L. A., Chen, J. RORalpha modulates semaphorin 3E transcription and neurovascular interaction in pathological retinal angiogenesis. |
