Heyden A, Lützow-Holm C, Clausen O P, Thrane E V, Brandtzaeg P, Roop D R, Yuspa S H, Huitfeldt H S
Institute of Pathology, University of Oslo, National Hospital, Norway.
Differentiation. 1994 Sep;57(3):187-93. doi: 10.1046/j.1432-0436.1994.5730187.x.
The tumour promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA) causes changes in epidermal protein expression, especially in the major differentiation products keratins K1 and K10. These keratins and filaggrin were studied in a pulse-labelled cell cohort in hairless mouse epidermis stimulated to proliferate by TPA or the hyperplasiogen cantharidin. Cells in DNA synthesis were pulse-labelled by 5-bromo-2-deoxyuridine (BrdU) 16 h after topical application of cantharidin or TPA. The BrdU-labelled cell cohort, the two keratins, and filaggrin were spatially mapped by paired immunofluorescence staining. Both cantharidin- and TPA-treated epidermis displayed altered distributions of K1 and K10 with expression only in the outermost cell layers, but the start of their postreplicative expression paralleled that in normal epidermis (18 h for K1 and 24 h for K10 after the last round of DNA synthesis). Cantharidin- and TPA-induced epidermal hyperplasia showed increased basal cell proliferation, accelerated suprabasal migration, and shortened transit time. Thus, the newly formed hyperplastic epidermis was composed of keratinocytes with a lower mean cellular age than that seen in unperturbed epidermis, which caused altered distribution of K1 and K10. Both hyperplastic and normal epidermis showed filaggrin expression in stratum granulosum; this started earlier in treated (30-36 h) than in untreated (96 h) skin. We concluded that the postmitotic onset of K1 and K10 expression was unaltered in regenerative epidermis, whereas filaggrin expression was considerably accelerated and thus influenced by the cell kinetic changes.
肿瘤促进剂12 - O - 十四烷酰佛波醇 - 13 - 乙酸酯（TPA）可引起表皮蛋白表达的变化，尤其是主要分化产物角蛋白K1和K10。在无毛小鼠表皮中，用TPA或增生剂斑蝥素刺激使其增殖，对一个脉冲标记的细胞群体中的这些角蛋白和丝聚蛋白进行了研究。在局部应用斑蝥素或TPA 16小时后，用5 - 溴 - 2 - 脱氧尿苷（BrdU）对处于DNA合成期的细胞进行脉冲标记。通过配对免疫荧光染色对BrdU标记的细胞群体、两种角蛋白和丝聚蛋白进行空间定位。斑蝥素和TPA处理的表皮均显示K1和K10的分布改变，仅在最外层细胞层表达，但其复制后表达的起始时间与正常表皮平行（最后一轮DNA合成后，K1为18小时，K10为24小时）。斑蝥素和TPA诱导的表皮增生表现为基底细胞增殖增加、基底上层迁移加速和转运时间缩短。因此，新形成的增生性表皮由平均细胞年龄低于未受干扰表皮的角质形成细胞组成，这导致了K1和K10分布的改变。增生性表皮和正常表皮在颗粒层均有丝聚蛋白表达；其在处理过的皮肤中（30 - 36小时）比未处理的皮肤中（96小时）开始得更早。我们得出结论，在再生表皮中，K1和K10表达的有丝分裂后起始时间未改变，而丝聚蛋白表达明显加速，因此受细胞动力学变化的影响。
