Purinergic substances promote murine keratinocyte proliferation and enhance impaired wound healing in mice.
As membrane-bound receptors for adenosine, purines, and pyrimidines, purinoceptors are expressed in nearly all cell types throughout the mammalian organism. Previous studies showed that purinoceptors are involved in the regulation of proliferation and differentiation of most target cells. The present study was performed to elucidate their role in keratinocyte proliferation and wound healing. The expression of the mRNA of several adenosine and P2Y receptors was shown in the immortalized murine keratinocyte cell line MSC-P5 and primary cultured keratinocytes of four different mouse strains. The nonselective adenosine receptor agonist 5'-(N-ethyl)-carboxamidoadenosine enhanced the growth of MSC-P5 cells in vitro via the A2B receptor. The proliferative stimulus of adenosine triphosphate and uridine triphosphate on this cell line was mediated by the P2Y2 receptor. The mitogenic effect of the purinergic substances was inhibited by simultaneous treatment with respective antagonists. Studies in a mouse model of dexamethasone-induced impaired wound healing showed the in vivo efficacy of the purinoceptor agonists. These studies confirm that pharmacological actions via purinoceptors offer an intriguing possibility in the treatment of impaired wound healing. Nevertheless, further investigations are needed to elucidate fully the role of purinergic mechanisms involved in wound healing.
Braun
Michael
M
Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine Hannover, Foundation, Hannover, Germany. michael.braun@tiho-hannover.de
Lelieur
Karin
K
Kietzmann
Manfred
M
D000255:Adenosine Triphosphate / Q000008:administration & dosage; D019830:Adenosine-5'-(N-ethylcarboxamide) / Q000008:administration & dosage; D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D005260:Female; D007150:Immunohistochemistry; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D011983:Receptors, Purinergic / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric; D013498:Suramin / Q000008:administration & dosage; D014530:Uridine Diphosphate / Q000008:administration & dosage; D014544:Uridine Triphosphate / Q000008:administration & dosage; D014945:Wound Healing / Q000187:drug effects* / Q000502:physiology; D014970:Xanthines / Q000008:administration & dosage
D011983:Receptors, Purinergic; D014970:Xanthines; D019830:Adenosine-5'-(N-ethylcarboxamide); D014530:Uridine Diphosphate; D013498:Suramin; D000255:Adenosine Triphosphate; C034347:enprofylline; D014544:Uridine Triphosphate