Human umbilical cord mesenchymal stem cells-derived exosomal microRNA-17-3p ameliorates inflammatory reaction and antioxidant injury of mice with diabetic retinopathy via targeting STAT1

Int Immunopharmacol. 2021 Jan:90:107010. doi: 10.1016/j.intimp.2020.107010. Epub 2020 Dec 14.

Abstract

Background: Accumulating evidence has reported the role of microRNA (miR) on diabetic retinopathy (DR). Thus, the aim of the study was to investigate the effect of exosomal miR-17-3p targeting signal transducer and activator of transcription 1 (STAT1) on inflammatory reaction and antioxidant injury of DR mice.

Methods: A mouse diabetes model was established and injected with miR-17-3p-containing human umbilical cord mesenchymal stem cells (hucMSCs)-derived exosomes to ascertain the role of exosomal miR-17-3p. The blood glucose, glycosylated hemoglobin (HbAlc), weight, hemoglobin (Hb) content, inflammatory factors, oxidative stress factors, vascular endothelial growth factor (VEGF), apoptosis index and glutamine synthetase (GS) level in serum and/or retinal tissues of DR mice were measured. miR-17-3p and STAT1 expression in retinal tissues as well as the target relationship between miR-17-3p and STAT1 were tested.

Results: miR-17-3p decreased and STAT1 increased in retinal tissues of DR mice, and STAT1 was the target gene of miR-17-3p. Injection of up-regulated exosomal miR-17-3p reduced the blood glucose and HbAlc, increased the weight, Hb content and GS level, decreased contents of inflammatory factors and VEGF, alleviated oxidative injury, and inhibited retinal cell apoptosis in DR mice through inhibiting STAT1.

Conclusion: Functional studies reveal that hucMSCs-derived exosomes shuffle miR-17-3p to ameliorate inflammatory reaction and oxidative injury of DR mice via targeting STAT1.

Keywords: Diabetic retinopathy; Exosomes; Signal transducer and activator of transcription 1; microRNA-17-3p.

MeSH terms

  • Animals
  • Apoptosis
  • Blood Glucose / metabolism
  • Cells, Cultured
  • Diabetic Retinopathy / genetics
  • Diabetic Retinopathy / metabolism
  • Diabetic Retinopathy / pathology
  • Diabetic Retinopathy / therapy*
  • Disease Models, Animal
  • Exosomes / genetics
  • Exosomes / metabolism
  • Exosomes / transplantation*
  • Glycated Hemoglobin / metabolism
  • Humans
  • Inflammation Mediators / metabolism*
  • Male
  • Mesenchymal Stem Cells / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Oxidative Stress*
  • Retina / metabolism*
  • Retina / pathology
  • STAT1 Transcription Factor / genetics
  • STAT1 Transcription Factor / metabolism*
  • Signal Transduction
  • Umbilical Cord / cytology

Substances

  • Blood Glucose
  • Glycated Hemoglobin A
  • HbA(1c) protein, mouse
  • Inflammation Mediators
  • MIRN17 microRNA, human
  • MicroRNAs
  • STAT1 Transcription Factor