Garmyn M, Degreef H, Gilchrest B A
Department of Dermatology, UZ Sint Rafael, Catholic University of Leuven, Belgium.
Dermatology. 1995;190(4):305-8. doi: 10.1159/000246722.
We identified genes involved in the normal response to acute UV damage, as they were modulated in cultured newborn keratinocytes by a single sublethal UV dose, appropriately filtered to mimic solar radiation. Their gene products encode proteins involved in the regulation of cell growth (proto-oncogenes c-myc and c-fos), a gene inducible by growth arrest and DNA damage (GADD153), the cytokine interleukin (IL) 1 alpha and beta and finally a differentiation-associated small proline-rich gene (SPR2). Because chronically sun-exposed skin is known to have altered immune responsiveness and a statistical predisposition to skin cancer, we then examined UV induction of these genes in cultured keratinocytes derived from habitually sun-exposed adult skin, and for the older donors in paired cultures derived from sun-protected site of the same donors. Aging alone increased the baseline expression of two differentiation-associated genes (SPR2 and IL-1 receptor antagonist) in cultures from sun-protected skin. In contrast, photoaging increased the UV inducibility of c-fos but decreased the baseline expression of the differentiation-associated genes IL-1 receptor antagonist and SPR2.
我们鉴定出了参与急性紫外线损伤正常反应的基因，因为它们在培养的新生角质形成细胞中受到单次亚致死紫外线剂量的调节，该剂量经过适当过滤以模拟太阳辐射。它们的基因产物编码参与细胞生长调节的蛋白质（原癌基因c-myc和c-fos）、一种可由生长停滞和DNA损伤诱导的基因（GADD153）、细胞因子白细胞介素（IL）1α和β，以及最后一个与分化相关的富含脯氨酸的小基因（SPR2）。由于已知长期暴露于阳光下的皮肤具有改变的免疫反应性以及患皮肤癌的统计学易感性，我们随后检测了这些基因在源自习惯性暴露于阳光的成人皮肤的培养角质形成细胞中的紫外线诱导情况，对于年长的供体，则检测了来自同一供体防晒部位的配对培养物中的情况。仅衰老就增加了来自防晒皮肤的培养物中两个与分化相关基因（SPR2和IL-1受体拮抗剂）的基线表达。相比之下，光老化增加了c-fos的紫外线诱导性，但降低了与分化相关基因IL-1受体拮抗剂和SPR2的基线表达。
