Modulation of keratinocyte proliferation by skin innervation

Several lines of evidence suggest that sensory nerves ending at the skin ha ve profound influences on their target, the epidermis. To test the hypothes is, we examined the consequences of denervation on the paw skin of rats by eliminating its innervation. We investigated temporal changes of nerve dege neration, keratinocyte proliferation and differentiation, gene expression, and epidermal thickness. Nerve terminals in the epidermis began to degenera te within 24 h after denervation, All epidermal nerves were completely dege nerated by 2 d, During the interval of nerve degeneration, there was a sign ificant reduction of bromodeoxyuridine incorporation from 24 h of nerve inj ury (39 +/- 7% of the control side, p 0.01), By 2 d, there was a further re duction of bromodeoxyuridine labeling (11 +/- 8%, p < 0.0001), The incorpor ation of bromodeoxyuridine remained depressed when the skin was denervated (35 +/- 11%, p < 0.01), Four days after eliminating skin innervation, the d enervated epidermis became thinner than the control epidermis (70 +/- 8% of the control, p < 0.01). Epidermal thinning was associated with a significa nt decrease in expression of glyceraldehyde-3-phosphate dehydrogenase and p -actin transcripts (33 +/- 8% of the control epidermis from postoperative d ay 4, p < 0.001). Other aspects of keratinocyte differentiation, including the patterns of keratin expression, and programmed cell death, were unalter ed by skin denervation, These data indicate that skin denervation is suffic ient to influence keratinocyte proliferation and therefore epidermal thickn ess.