Diabetes leads to impairment of the normal course of wound healing. Interestingly, recent
studies have implicated a critical role of P2X/P2Y nucleotide receptors in dermal tissue regeneration
and maintaining vascular homeostasis. As new vessel generation and keratinization process are decreased
in diabetic patients we determined whether nucleoside 5'-O-phosphorothioate analogues might
accelerate vascular endothelial growth factor (VEGF) production as well as the growth and migration
of human keratinocytes under hyperglycaemic conditions. We also investigated the expression pattern
of P2X/P2Y receptors in human keratinocyte HaCaT cells. We show here that nucleoside 5'-Ophosphorothioate
analogues are better candidates to overcome hyperglycaemia-induced impairment of angiogenesis as
compared to their unmodified counterparts. The greatest potency for VEGF release and stimulation of cell migration by
thiophosphate analogues of ATP and UTP correlates with the highest P2Y2 receptor expression by HaCaT cells. We also
found that UTPαS significantly increased the viability and proliferation of the HaCaT cells. These findings suggest that
thiophosphate analogues of nucleotides could serve as potential therapeutic agents for promoting impaired angiogenesis
under diabetic conditions.
Keywords: Angiogenesis, Hyperglycaemia, Keratinocytes, Nucleoside-5'-O-phosphorothioate analogues, P2Y receptors,
VEGF, Wound healing.
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