Extracellular Nucleotides Affect the Proangiogenic Behavior of Fibroblasts,Keratinocytes, and Endothelial Cells |
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| Authors: | Edyta W&#x;g&#x;owska Maria Kozio&#x;kiewicz Daria Kami&#x;ska Bart&#x;omiej Grobelski Dariusz Pawe&#x;czak Marek Ko&#x;odziejczyk Stanis&#x;aw Bielecki Edyta Gendaszewska-Darmach |
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| Affiliation: | 1.Institute of Molecular and Industrial Biotechnology, Faculty of Biotechnology and Food Sciences, Lodz University of Technology, Stefanowskiego 2/22, 90-537 Lodz, Poland; (E.W.); (M.K.); (D.K.); (M.K.); (S.B.);2.Department of Experimental Surgery, Medical University of Lodz, 93-513 Lodz, Poland; (B.G.); (D.P.) |
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| Abstract: | Chronic wound healing is currently a severe problem due to its incidence and associated complications. Intensive research is underway on substances that retain their biological activity in the wound microenvironment and stimulate the formation of new blood vessels critical for tissue regeneration. This group includes synthetic compounds with proangiogenic activity. Previously, we identified phosphorothioate analogs of nucleoside 5′-O-monophosphates as multifunctional ligands of P2Y6 and P2Y14 receptors. The effects of a series of unmodified and phosphorothioate nucleotide analogs on the secretion of VEGF from keratinocytes and fibroblasts, as well as their influence on the viability and proliferation of keratinocytes, fibroblasts, and endothelial cells were analyzed. In addition, the expression profiles of genes encoding nucleotide receptors in tested cell models were also investigated. In this study, we defined thymidine 5′-O-monophosphorothioate (TMPS) as a positive regulator of angiogenesis. Preliminary analyses confirmed the proangiogenic potency of TMPS in vivo. |
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| Keywords: | extracellular nucleotides angiogenesis purinergic receptors phosphorothioate analogs |
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