Long Non-coding RNA SPAG5-AS1 Attenuates Diabetic Retinal Vascular Dysfunction by Inhibiting Human Retinal Microvascular Endothelial Cell Proliferation, Migration, and Tube Formation by Regulating the MicroRNA-1224-5p/IRS-1 Axis

Mol Biotechnol. 2023 Jun;65(6):904-912. doi: 10.1007/s12033-022-00572-3. Epub 2022 Nov 8.

Abstract

Diabetic retinopathy (DR) is causal for visual impairment and blindness. The research aimed at whether and how lncRNA SPAG5-AS1 (SPAG5-AS1) is involved in retinal vascular dysfunction under diabetic conditions. After determination of SPAG5-AS1, miR-1224-5p, and IRS-1 expression in high glucose (HG)-treated human retinal microvascular endothelial cells (hRMECs), their respective influences on retinal vascular dysfunction was explored by cell counting kit-8, Transwell, wound-healing assay, and tube formation assay. SPAG5-AS1/miR-1224-5p/IRS-1 interaction was identified through bioinformatics analysis and luciferase reporter gene assays. As tested, SPAG5-AS1 and IRS-1 levels were induced, while miR-1224-5p was enhanced in HG-treated hRMECs. Up-regulating SPAG5-AS1 or downregulating miR-1224-5p could inhibit hRMECs proliferation, migration, and tube formation, and vice versa. SPAG5-AS1 can promote IRS-1 expression by miR-1224-5p, and depletion of IRS-1 was functional for the reversal of up-regulated SPAG5-AS1-modified influences on HG-treated hRMECs. Additionally, in diabetic rats, SPAG5-AS1 can alleviate retinal vascular dysfunction. All in all, SPAG5-AS1 attenuates diabetic retinal vascular dysfunction through miR-1224-5p/IRS-1 axis, providing a potential therapeutic strategy for DR.

Keywords: Capillary; Diabetic retinopathy; Luciferase.

MeSH terms

  • Animals
  • Cell Cycle Proteins / metabolism
  • Cell Proliferation / genetics
  • Diabetes Mellitus, Experimental* / complications
  • Diabetes Mellitus, Experimental* / genetics
  • Diabetes Mellitus, Experimental* / metabolism
  • Diabetic Retinopathy* / genetics
  • Diabetic Retinopathy* / metabolism
  • Endothelial Cells / metabolism
  • Humans
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism
  • Rats

Substances

  • RNA, Long Noncoding
  • MicroRNAs
  • SPAG5 protein, human
  • Cell Cycle Proteins
  • MIRN1224 microRNA, human