Liou A, Elias P M, Grunfeld C, Feingold K R, Wood L C
Clinical Pharmacy, University Paris XI, France.
J Invest Dermatol. 1997 Jan;108(1):73-7. doi: 10.1111/1523-1747.ep12285638.
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.
溶剂或胶带剥离破坏小鼠的渗透屏障会刺激一种稳态修复反应，其中包括表皮DNA合成增加。为了确定DNA合成增加的潜在介质，我们在急性屏障破坏后测量了编码各种生长因子的mRNA的表皮水平。在本研究中，双调蛋白和神经生长因子的mRNA在胶带剥离后30分钟均显示比对照组增加，在1 - 2小时达到峰值水平，为对照组的12至30倍，并在6小时后恢复到对照水平。在另一种不相关的屏障破坏形式即丙酮处理后，观察到双调蛋白和神经生长因子mRNA增加的时间进程相似。此外，在丙酮处理破坏屏障后立即用乳胶封闭人工恢复屏障，抑制了表皮双调蛋白和神经生长因子mRNA水平的增加，表明屏障状态调节这些生长因子的产生。相比之下，抑制性生长因子转化生长因子-β1的mRNA水平在早期没有变化，在胶带剥离后6小时下降了53%（p < 0.02），而转化生长因子-α的mRNA水平在急性屏障破坏后的所有时间都保持不变。这些结果表明屏障破坏刺激了双调蛋白和神经生长因子的表达。这些角质形成细胞生长和分化的调节因子共同作用，可能是与屏障破坏相关的增殖反应增加的原因。
