UTP increases wound healing in the self assembled skin substitute (SASS)

Abstract

The therapeutic potential of purinergic signaling has been explored for a wide variety of diseases, including those related to the skin. In this study, we used the self‐assembled skin substitutes (SASS), a highly functional reconstructed human skin model, which shares many properties with normal human skin, to study the impact of purinergic receptors agonists, such as ATP, UTP and a P2Y receptor antagonist, Reactive Blue 2 during wound healing. After treating the wounded skins, we evaluated the wound area, reepithelialization, length of migrating tongues toward the wound, quality of the skins through the cytokeratin 10 and laminin‐5 expression, epidermal and dermal cell proliferation. In addition, the expression of the main ectoenzymes capable of hydrolyzing nucleotides were investigated through the wounded SASS regions: unwounded region, wound margin, intermediate region and migrating epidermal tongue. After 3 days, under the UTP treatment, the wounded SASS showed an increase in the reepithelialization and in the proliferation of keratinocytes and fibroblasts, without altering the quality of the skin. We also identified the presence of the ectoenzymes NTPDase1 and NPP1 in the reconstructed human skin model, suggesting their involvement in wound healing. Considering the need for new therapies capable of promoting healing in complex wounds, although these results are still preliminary, they suggest the involvement of extracellular nucleotides in human skin healing and the importance to understand their role in this mechanism. New experiments it will be necessary to determine the mechanisms by which the purinergic signaling is involved in the skin wound healing.

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.…”