Extracellular Nucleotides Affect the Proangiogenic Behavior of Fibroblasts, Keratinocytes, and Endothelial Cells

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.

Immunomodulation of wound healing leading to efferocytosis

“…� Regulates angiogenesis 32 � Promotes proliferation and migration of fibroblasts 33 � Promotes collagen deposition 34 � Accelerates wound closure 35 � Regulates angiogenesis 36 � Immune cell phenotype that promotes regeneration 37 � Promotes cell proliferation 38 � Promotes collagen deposition 39 � Increased proliferation of keratinocytes and fibroblasts 40 � Regulates angiogenesis 41 Bind Eat me signal Phosphatidylserine (PtdSer) Calreticulin (CRT) Thrombospondin 1 (TSP1) Milk fat globule-EGF-factor 8 (MFG-E8) Gas6 Protein S � Participate in hemostasis 42 � Promotes the resolution of inflammation 43 � Ca 2þ homeostasis in vivo 44 � Induces migration of pro-repair cells 45 � Promotes re-epithelialization 46 � Regulates fibroblast secretion and collagen deposition 47 � Regulates cell migration and matrix remodeling 48 � Regulates blood clotting and promotes angiogenesis 49 � Promote the migration and proliferation of fibroblasts 50 � Regulates angiogenesis 51 � None Bridge molecules in the dermis, DCs, macrophages, and T cells predominate. 54 An important step in wound repair is the elimination of cell death induced by the inflammatory environment.…”

Determination of Non-Cytotoxic Concentrations of Purine Analogues on Different Types of In Vitro-Incubated Embryonic Cells: A Pilot Study

“…The influence of many nucleotide analogs on the secretion of vascular endothelial growth factor (VEGF) by keratinocytes and fibroblasts, but also their influence on the viability and proliferation of keratinocytes, fibroblasts and endothelial cells have also been analyzed [19]. Nucleotide metabolism supports the processes of DNA-replication and RNA-synthesis, enabling in this way cell growth and division/proliferation, which have been inhibited in nucleotide depletion and disbalance [20].…”

Mechanism and application of β‐adrenoceptor blockers in soft tissue wound healing

“…Soft tissue wound healing involves a cascade of biological events in which cells and cytokines interact with the extracellular matrix 14 . The sequence of events are guided by growth factors and chemokines secreted by cells participating in the healing process 15 .…”

“…13 Soft tissue wound healing involves a cascade of biological events in which cells and cytokines interact with the extracellular matrix. 14 The sequence of events are guided by growth factors and chemokines secreted by cells participating in the healing process. 15 The wound healing process can be divided into three overlapping phases: vascular response and inflammation phase, proliferation phase, and tissue remodeling phase.…”