Amphiregulin and Nerve Growth Factor Expression Are Regulated by Barrier Status in Murine Epidermis

Abstract

Disruption of the murine permeability barrier by solvents or tape stripping stimulates a homeostatic repair response that includes increased epidermal DNA synthesis. To identify potential mediators of the increase in DNA synthesis, we have measured epidermal levels of mRNAs encoding various growth factors after acute barrier disruption. In this study, mRNAs for amphiregulin and nerve growth factor were each shown to increase over controls at 30 min, reach peak levels of 12- to 30-fold at 1-2 h, and return to control levels by 6 h after tape stripping. A similar time course for the increase of amphiregulin and nerve growth factor mRNAs was observed after an unrelated form of barrier disruption, i.e., acetone treatment. Furthermore, artificial restoration of the barrier by Latex occlusion, immediately following barrier disruption by acetone treatment, inhibited the increase in epidermal amphiregulin and nerve growth factor mRNA levels, indicating that barrier status regulates the production of these growth factors. In contrast, mRNA levels of transforming growth factor-beta1, an inhibitory growth factor, were unchanged at early times and decreased by 53% (p < 0.02) 6 h after tape stripping, whereas mRNA levels of transforming growth factor-alpha remained unchanged at all times after acute barrier disruption. These results suggest that barrier disruption stimulates the expression of amphiregulin and nerve growth factor. Together, these regulators of keratinocyte growth and differentiation may be responsible for the increased proliferative response that is associated with barrier disruption.