Pietilä Marko, Pirinen Eija, Keskitalo Salla, Juutinen Sisko, Pasonen-Seppänen Sanna, Keinänen Tuomo, Alhonen Leena, Jänne Juhani
A.I. Virtanen Institute for Molecular Sciences, University of Kuopio, Kuopio, Finland.
J Invest Dermatol. 2005 Mar;124(3):596-601. doi: 10.1111/j.0022-202X.2005.23636.x.
Overexpression of the rate-limiting enzyme in polyamine catabolism spermidine/spermine N1-acetyltransferase (SSAT) in transgenic (Tg) mouse leads to accumulation of putrescine in the skin and permanent hair loss at the age of 3 wk. The hair follicles of these mice are replaced by dermal cysts and epidermal utriculi. Increased putrescine production is also seen in hyperproliferative cutaneous disorders such as in psoriasis. These disorders are characterized by delayed onset of epidermal differentiation characterized as reduced expression of terminal differentiation markers such as cytokeratins 1/10, and filaggrin and persisting expression of basal cell cytokeratins 5/14 in the suprabasal layers. The use of these markers in immunohistological analysis of SSAT Tg skin clearly showed signs of disturbed differentiation. To exclude the possibility that changes in differentiation originated from underlying connective tissue, we introduced SSAT gene into an established rat epidermal cell line. Organotypic cultures derived from the transfected cells displayed similar changes in their differentiation pattern as keratinocytes in Tg skin. The role of accumulated putrescine in cutaneous changes of SSAT Tg mice was verified by an experiment in which putrescine level was reduced by systemic putrescine biosynthesis inhibition. The putrescine reduction was sufficient to alleviate the cutaneous changes to such an extent that distinct hair regrowth could be seen. These results suggest that the cutaneous changes of SSAT Tg animals are due to disorders of the keratinocyte differentiation. Moreover, they strengthen the view that the proper regulation of polyamine metabolism plays an important role in the keratinocyte maturation.
多胺分解代谢限速酶亚精胺/精胺N1 - 乙酰基转移酶（SSAT）在转基因（Tg）小鼠中的过表达，导致皮肤中腐胺积累，并在3周龄时出现永久性脱毛。这些小鼠的毛囊被真皮囊肿和表皮小囊所取代。在银屑病等增殖性皮肤病中也可见腐胺生成增加。这些疾病的特征是表皮分化延迟，表现为终末分化标志物如细胞角蛋白1/10和丝聚蛋白的表达降低，以及基底细胞角蛋白5/14在基底层以上持续表达。在SSAT转基因皮肤的免疫组织学分析中使用这些标志物，清楚地显示出分化紊乱的迹象。为了排除分化变化源于潜在结缔组织的可能性，我们将SSAT基因导入已建立的大鼠表皮细胞系。源自转染细胞的器官型培养物在分化模式上表现出与转基因皮肤中的角质形成细胞相似的变化。通过全身性抑制腐胺生物合成来降低腐胺水平的实验，证实了积累的腐胺在SSAT转基因小鼠皮肤变化中的作用。腐胺水平的降低足以缓解皮肤变化，以至于可以看到明显的毛发生长。这些结果表明，SSAT转基因动物的皮肤变化是由于角质形成细胞分化紊乱所致。此外，它们强化了这样一种观点，即多胺代谢的适当调节在角质形成细胞成熟中起重要作用。
