title: miR-23b-3p induces the cellular metabolic memory of high glucose in diabetic retinopathy through a SIRT1-dependent signalling pathway.
abstract: OBJECTIVE
  The mechanisms underlying the cellular metabolic memory induced by high glucose remain unclear. Here, we sought to determine the effects of microRNAs (miRNAs) on metabolic memory in diabetic retinopathy.
  
  
  METHODS
  The miRNA microarray was used to examine human retinal endothelial cells (HRECs) following exposure to normal glucose (N) or high glucose (H) for 1 week or transient H for 2 days followed by N for another 5 days (H→N). Levels of sirtuin 1 (SIRT1) and acetylated-nuclear factor κB (Ac-NF-κB) were examined following transfection with miR-23b-3p inhibitor or with SIRT1 small interfering (si)RNA in the H→N group, and the apoptotic HRECs were determined by flow cytometry. Retinal tissues from diabetic rats were similarly studied following intravitreal injection of miR-23b-3p inhibitor. Chromatin immunoprecipitation (ChIP) analysis was performed to detect binding of NF-κB p65 to the potential binding site of the miR-23b-27b-24-1 gene promoter in HRECs.
  
  
  RESULTS
  High glucose increased miR-23b-3p expression, even after the return to normal glucose. Luciferase assays identified SIRT1 as a target mRNA of miR-23b-3p. Reduced miR-23b-3p expression inhibited Ac-NF-κB expression by rescuing SIRT1 expression and also relieved the effect of metabolic memory induced by high glucose in HRECs. The results were confirmed in the retina using a diabetic rat model of metabolic memory. High glucose facilitated the recruitment of NF-κB p65 and promoted transcription of the miR-23b-27b-24-1 gene, which can be suppressed by decreasing miR-23b-3p expression.
  
  
  CONCLUSIONS
  These studies identify a novel mechanism whereby miR-23b-3p regulates high-glucose-induced cellular metabolic memory in diabetic retinopathy through a SIRT1-dependent signalling pathway.
authors.affiliation: Department of Ophthalmology, Shanghai First People's Hospital Affiliated to Shanghai Jiao Tong University, Haining Road 100, Shanghai, 200080, People's Republic of China.
authors.forename: Shuzhi
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Department of Ophthalmology, Shanghai First People's Hospital Affiliated to Shanghai Jiao Tong University, Haining Road 100, Shanghai, 200080, People's Republic of China.
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Ophthalmology, Lishui City Center Hospital, Lishui, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Ophthalmology, Shanghai First People's Hospital Affiliated to Shanghai Jiao Tong University, Haining Road 100, Shanghai, 200080, People's Republic of China.
authors.forename: Qianyi
authors.initials: Q
authors.lastname: Lu
authors.affiliation: Department of Ophthalmology, Shanghai First People's Hospital Affiliated to Shanghai Jiao Tong University, Haining Road 100, Shanghai, 200080, People's Republic of China.
authors.forename: Changjing
authors.initials: C
authors.lastname: Han
authors.affiliation: Department of Ophthalmology, Shanghai First People's Hospital Affiliated to Shanghai Jiao Tong University, Haining Road 100, Shanghai, 200080, People's Republic of China.
authors.forename: Na
authors.initials: N
authors.lastname: Wang
authors.affiliation: Department of Ophthalmology, Shanghai First People's Hospital Affiliated to Shanghai Jiao Tong University, Haining Road 100, Shanghai, 200080, People's Republic of China.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Qiu
authors.affiliation: Department of Ophthalmology, Shanghai First People's Hospital Affiliated to Shanghai Jiao Tong University, Haining Road 100, Shanghai, 200080, People's Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Cao
authors.affiliation: Department of Ophthalmology, Shanghai First People's Hospital Affiliated to Shanghai Jiao Tong University, Haining Road 100, Shanghai, 200080, People's Republic of China.
authors.forename: Xun
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Endocrinology and Metabolism, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University, Yishan Road 301, Shanghai, 200233, People's Republic of China. chenhb@sjtu.edu.cn.
authors.forename: Haibing
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Ophthalmology, Shanghai First People's Hospital Affiliated to Shanghai Jiao Tong University, Haining Road 100, Shanghai, 200080, People's Republic of China. zzheng88@sjtu.edu.cn.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Zheng
mesh_terms: D000818:Animals; D002460:Cell Line; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D003930:Diabetic Retinopathy / Q000235:genetics / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism*
chemical_list: C552430:MIRN23a microRNA, human; D035683:MicroRNAs; D056564:Sirtuin 1; D005947:Glucose
keywords: Diabetic retinopathy; Metabolic memory; NF-κB; SIRT1; miR-23b-3p