AMPHIREGULIN AND NERVE GROWTH-FACTOR EXPRESSION ARE REGULATED BY BARRIER STATUS IN MURINE EPIDERMIS

Disruption of the murine permeability barrier by solvents or tape stri pping stimulates a homeostatic repair response that includes increased epidermal DNA synthesis. To identify potential mediators of the incre ase in DNA synthesis, we have measured epidermal levels of mRNAs encod ing various growth factors after acute barrier disruption. In this stu dy, 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 disruptio n, 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 r egulates the production of these growth factors, In contrast, mRNA lev els of transforming growth factor-beta 1, an inhibitory growth factor, were unchanged at early times and decreased by 53% (p < 0.02) 6 h aft er tape stripping, whereas mRNA levels of transforming growth factor-a lpha remained unchanged at all times after acute barrier disruption. T hese results suggest that barrier disruption stimulates the expression of amphiregulin and nerve growth factor, Together, these regulators o f keratinocyte growth and differentiation may be responsible for the i ncreased proliferative response that is associated with barrier disrup tion.