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Proangiogenic properties of nucleoside 5'-O-phosphorothioate analogues under hyperglycaemic conditions

Edyta Węgłowska, Marcin Szustak, Edyta Gendaszewska-Darmach1

  • 1Institute of Technical Biochemistry, Faculty of Biotechnology and Food Sciences, Lodz University of Technology, Stefanowskiego 4/10, 90-924 Lodz, Poland. edarmach@wp.pl.

Current Topics in Medicinal Chemistry
|June 20, 2015
PubMed

Insights

Nucleotide analogues accelerate wound healing in diabetes by enhancing vascular endothelial growth factor (VEGF) production and keratinocyte migration. These compounds show promise for treating diabetic complications.

Area of Science:

  • Biomedical Science
  • Wound Healing Research
  • Diabetic Complications

Background:

  • Diabetes mellitus impairs wound healing, affecting dermal regeneration and vascular homeostasis.
  • P2X/P2Y nucleotide receptors play a crucial role in tissue repair and blood vessel formation.
  • Hyperglycemia in diabetes reduces new blood vessel generation and keratinization.

Purpose of the Study:

  • To investigate if nucleoside 5'-O-phosphorothioate analogues can enhance vascular endothelial growth factor (VEGF) production.
  • To determine the effect of these analogues on human keratinocyte growth and migration under hyperglycemic conditions.
  • To examine the expression of P2X/P2Y receptors in human keratinocyte (HaCaT) cells.

Main Methods:

  • Treatment of HaCaT cells with nucleoside 5'-O-phosphorothioate analogues under hyperglycemic conditions.
  • Measurement of VEGF production and assessment of keratinocyte proliferation and migration.
  • Analysis of P2X/P2Y receptor expression patterns in HaCaT cells.

Main Results:

  • Nucleoside 5'-O-phosphorothioate analogues effectively counteracted hyperglycemia-induced impairment of angiogenesis.
  • Thiophosphate analogues of ATP and UTP demonstrated significant potency in promoting VEGF release and cell migration.
  • UTPαS notably enhanced HaCaT cell viability and proliferation.
  • The efficacy of thiophosphate analogues correlated with high P2Y2 receptor expression in HaCaT cells.

Conclusions:

  • Nucleoside 5'-O-phosphorothioate analogues are superior to unmodified versions in improving angiogenesis under diabetic conditions.
  • These analogues hold potential as therapeutic agents for accelerating wound healing in diabetic patients.
  • Targeting P2Y2 receptors with thiophosphate nucleotide analogues may offer a novel treatment strategy for diabetic-related vascular impairments.

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