The mechanism by which crocetin regulates the lncRNA NEAT1/miR-125b-5p/SOX7 molecular axis to inhibit high glucose-induced diabetic retinopathy

Exp Eye Res. 2022 Sep:222:109157. doi: 10.1016/j.exer.2022.109157. Epub 2022 Jun 16.

Abstract

Diabetic retinopathy (DR) is a high-incidence microvascular complication with retinal neovascularization that generates irreversible visual impairment. However, the mechanism of DR is unclear and needs to be further explored. To explore the the effects of crocetin on expression of NEAT1 and miR-125b-5p and the proliferation activity, migration ability, and angiogenesis ability of human retinal microvascular endothelial cells (hRMECs), RT-qPCR, CCK-8, Transwell, and tube formation assays were performed. Additionally, Western blot was used to detect the expression of SOX7, VEGFA and CD31. Furthermore, a dual-luciferase reporter gene was used to verify the targeting connection. The DR mouse model was constructed by STZ. The effect of crocetin on DR angiogenesis was detected by hematoxylin-eosin (HE) staining, immunohistochemistry (IHC), retinal digest preparations and Western blot. The results showed that crocetin inhibited the high-glucose (Hg)-induced upregulation of NEAT1 and SOX7 and the downregulation of miR-125b-5p. Crocetin inhibited Hg-induced proliferation, migration and angiogenesis by upregulating the targeted inhibition of SOX7 by miR-125b-5p through the inhibition of NEAT1. To summarize, our study revealed that crocetin has a protective effect on Hg-induced DR by regulating the lncRNA NEAT1/miR-125b-5p/SOX7 molecular axis.

Keywords: Diabetic retinopathy; LncRNA; NEAT1; Neovascularization; SOX7; miR-125b-5p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carotenoids
  • Cell Proliferation
  • Diabetes Mellitus* / metabolism
  • Diabetic Retinopathy* / drug therapy
  • Diabetic Retinopathy* / genetics
  • Diabetic Retinopathy* / metabolism
  • Endothelial Cells / metabolism
  • Glucose / metabolism
  • Glucose / toxicity
  • Humans
  • Mice
  • MicroRNAs* / genetics
  • Neovascularization, Pathologic / metabolism
  • RNA, Long Noncoding* / genetics
  • SOXF Transcription Factors / metabolism
  • Vitamin A / analogs & derivatives

Substances

  • MIRN125 microRNA, human
  • MicroRNAs
  • NEAT1 long non-coding RNA, human
  • RNA, Long Noncoding
  • SOX7 protein, human
  • SOXF Transcription Factors
  • Sox7 protein, mouse
  • trans-sodium crocetinate
  • Vitamin A
  • Carotenoids
  • Glucose