RORα modulates semaphorin 3E transcription and neurovascular interaction in pathological retinal angiogenesis.

Autor:	Sun Y; Department of Ophthalmology, Harvard Medical School, Boston Children's Hospital, Boston, Massachusetts, USA., Liu CH; Department of Ophthalmology, Harvard Medical School, Boston Children's Hospital, Boston, Massachusetts, USA., Wang Z; Department of Ophthalmology, Harvard Medical School, Boston Children's Hospital, Boston, Massachusetts, USA., Meng SS; Department of Ophthalmology, Harvard Medical School, Boston Children's Hospital, Boston, Massachusetts, USA., Burnim SB; Department of Ophthalmology, Harvard Medical School, Boston Children's Hospital, Boston, Massachusetts, USA., SanGiovanni JP; Section of Nutritional Neuroscience, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, USA.; Department of Biochemistry and Molecular and Cellular Biology, Georgetown School of Medicine, Washington, D.C., USA., Kamenecka TM; Department of Molecular Medicine, The Scripps Research Institute, Jupiter, Florida, USA., Solt LA; Department of Immunology and Microbiology, The Scripps Research Institute, Jupiter, Florida, USA., Chen J; Department of Ophthalmology, Harvard Medical School, Boston Children's Hospital, Boston, Massachusetts, USA; jing.chen@childrens.harvard.edu.
Jazyk:	angličtina
Zdroj:	FASEB journal : official publication of the Federation of American Societies for Experimental Biology [FASEB J] 2017 Oct; Vol. 31 (10), pp. 4492-4502. Date of Electronic Publication: 2017 Jun 23.
DOI:	10.1096/fj.201700172R
Abstrakt:	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 α (RORα), 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 RORα substantially induced Sema3e expression in retinopathy. Both RORα and SEMA3E were expressed in retinal ganglion cells. RORα 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 RORα deficiency in retinopathy. Our findings suggest that RORα 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. RORα modulates semaphorin 3E transcription and neurovascular interaction in pathological retinal angiogenesis. (© FASEB.)
Databáze:	MEDLINE
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