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Nrf2 in ischemic neurons promotes retinal vascular regeneration through regulation of semaphorin 6A #MMPMID26621751
Wei Y; Gong J; Xu Z; Thimmulappa RK; Mitchell KL; Welsbie DS; Biswal S; Duh EJ
Proc Natl Acad Sci U S A 2015[Dec]; 112 (50): E6927-36 PMID26621751show ga
Delayed revascularization of ischemic neural tissue is a major impediment to preservation of function in central nervous system (CNS) diseases including stroke and ischemic retinopathies. The key mechanisms governing vascular recovery in ischemic CNS, including regulatory molecules governing transition from tissue injury to repair, are largely unknown. We report here on NF-E2-related factor 2 (Nrf2), a major stress-response transcription factor known for its cell-intrinsic cytoprotective function, in a novel capacity coordinating tissue repair and remodeling, including regulation of cell?cell crosstalk. Nrf2 activity in ischemic neurons reduces their resistance to reparative angiogenesis by suppressing expression of neuronal semaphorin 6A (Sema6A) and its antiangiogenic effects. Pharmacologic activation of Nrf2 or inhibition of Sema6A promote reparative angiogenesis in this ischemic setting, suggesting therapeutic avenues for ischemic retinopathies and other ischemic diseases.