title: microRNA-182 Mediates Sirt1-Induced Diabetic Corneal Nerve Regeneration.
abstract: Sensory neurons are particularly susceptible to neuronal damage in diabetes, and silent mating type information regulation 2 homolog 1 (Sirt1) has been recently identified as a key gene in neuroprotection and wound healing. We found that the expression of Sirt1 was downregulated in trigeminal sensory neurons of diabetic mice. A microRNA microarray analysis identified microRNA-182 (miR-182) as a Sirt1 downstream effector, and the expression level of miR-182 was increased by Sirt1 overexpression in trigeminal neurons; Sirt1 bound to the promoter of miR-182 and regulated its transcription. We also revealed that miR-182 enhanced neurite outgrowth in isolated trigeminal sensory neurons and overcame the detrimental effects of hyperglycemia by stimulating corneal nerve regeneration by decreasing the expression of one of its target genes, NOX4. Furthermore, the effects of miR-182 on corneal nerve regeneration are associated with a functional recovery of corneal sensation in hyperglycemic conditions. These data demonstrate that miR-182 is a key regulator in diabetic corneal nerve regeneration through targeting NOX4, suggesting that miR-182 might be a potential target for the treatment of diabetic sensory nerve regeneration and diabetic keratopathy.
authors.affiliation: State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong Academy of Medical Sciences, Qingdao, China wye112002@126.com lixin_xie@hotmail.com.
authors.forename: Ye
authors.initials: Y
authors.lastname: Wang
authors.affiliation: State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong Academy of Medical Sciences, Qingdao, China.
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Zhao
authors.affiliation: State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong Academy of Medical Sciences, Qingdao, China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Wu
authors.affiliation: State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong Academy of Medical Sciences, Qingdao, China.
authors.forename: Yunhai
authors.initials: Y
authors.lastname: Dai
authors.affiliation: State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong Academy of Medical Sciences, Qingdao, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Chen
authors.affiliation: State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong Academy of Medical Sciences, Qingdao, China wye112002@126.com lixin_xie@hotmail.com.
authors.forename: Lixin
authors.initials: L
authors.lastname: Xie
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003315:Cornea / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism; D009416:Nerve Regeneration / Q000235:genetics*; D009474:Neurons / Q000378:metabolism; D011401:Promoter Regions, Genetic; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism*; D014945:Wound Healing / Q000502:physiology
chemical_list: D035683:MicroRNAs; C540524:Mirn182 microRNA, mouse; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C422943:Nox4 protein, mouse; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1