Abstract
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.
Current Topics in Medicinal Chemistry
Title:Proangiogenic Properties of Nucleoside 5'-O-Phosphorothioate Analogues Under Hyperglycaemic Conditions
Volume: 15 Issue: 23
Author(s): Edyta Węgłowska, Marcin Szustak and Edyta Gendaszewska-Darmach
Affiliation:
Keywords: Angiogenesis, Hyperglycaemia, Keratinocytes, Nucleoside-5'-O-phosphorothioate analogues, P2Y receptors, VEGF, Wound healing.
Abstract: 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.
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Węgłowska Edyta, Szustak Marcin and Gendaszewska-Darmach Edyta, Proangiogenic Properties of Nucleoside 5'-O-Phosphorothioate Analogues Under Hyperglycaemic Conditions, Current Topics in Medicinal Chemistry 2015; 15 (23) . https://dx.doi.org/10.2174/1568026615666150619142859
DOI https://dx.doi.org/10.2174/1568026615666150619142859 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
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