Regulation of eNOS in normal and diabetes-impaired skin repair: implications for tissue regeneration.
An important role of inducible nitric oxide (NO) synthase for epithelial action during skin repair has been well established. Although a delayed healing of skin wounds has been recently described for eNOS-deficient mice, a participation of endothelial-type NO synthase (eNOS) in skin repair largely remains unclear. In this study we determined the expression pattern of eNOS during wound healing in healthy and in diabetic mice. Remarkably, normal repair in healthy animals was characterized by a moderate induction of eNOS at the mRNA and protein level, whereas diabetes-impaired healing was associated with a clearly reduced eNOS protein expression. Immunohistochemistry revealed the endothelial lining of blood vessels within the granulation tissue, and also keratinocytes of the wound margins, the developing neo-epithelium, and the hair follicles to express eNOS protein. Keratinocyte-derived expression of eNOS could be confirmed at the mRNA level in vitro for human primary keratinocytes and the keratinocyte cell line HaCaT. Furthermore, eNOS enzymatic activity most likely contributes to epithelial regeneration, as eNOS-deficient (eNOS -/-) animals exhibited reduced wound margin epithelia associated with reduced keratinocyte proliferation.
Stallmeyer
Birgit
B
Pharmazentrum Frankfurt, Klinikum der Johann Wolfgang Goethe-Universität, Theodor-Stern-Kai 7, D-60590 Frankfurt am Main, Germany.
Anhold
Manuel
M
Wetzler
Christian
C
Kahlina
Kornelija
K
Pfeilschifter
Josef
J
Frank
Stefan
S
D000818:Animals; D001808:Blood Vessels / Q000201:enzymology; D003920:Diabetes Mellitus / Q000201:enzymology* / Q000378:metabolism; D004195:Disease Models, Animal; D004790:Enzyme Induction / Q000502:physiology; D005260:Female; D015603:Keratinocytes / Q000201:enzymology; D051379:Mice; D008810:Mice, Inbred C57BL; D019001:Nitric Oxide Synthase / Q000096:biosynthesis* / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D012333:RNA, Messenger / Q000096:biosynthesis; D012038:Regeneration; D012867:Skin / Q000201:enzymology* / Q000378:metabolism; D012879:Skin Physiological Phenomena; D014945:Wound Healing / Q000502:physiology*
D012333:RNA, Messenger; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse