Epidermal growth control in psoriasis and normal skin

我们的皮肤保护我们免受伤害、脱水、感染和有害的紫外线辐射。同时，我们希望它保持健康、顺畅和良好的外观。皮肤，更具体地说，它的上层，表皮，如何适应所有这些要求是一个复杂的问题，还没有完全弄清楚。这个问题构成了我们项目提案的基础。表皮是一种不断自我更新的组织，其中的细胞在看不见地脱落到外面之前，平均寿命为30天。在正常状态下，当对损伤或疾病做出反应时，这种细胞周转速度可以被微调，例如在伤口愈合的情况下加速。相比之下，如果受到阳光的破坏，表皮细胞会经历一种形式的细胞自杀(凋亡)，以防止带有受损基因的细胞形成肿瘤。这种变化的周转速度受一系列增长因素或细胞因子的控制。胰岛素样生长因子-I(IGF-I)是一种独特的细胞因子，既能控制细胞周转率，又能控制细胞死亡。我们的目标是揭示复杂的生化相互作用，使表皮IGF-I系统完成这一看似矛盾的任务。这项研究很重要，因为当表皮失去微调周转速度的能力时，就会出现溃疡、阳光损伤、常见的皮肤病牛皮癣，或者更糟糕的是，皮肤肿瘤。这个项目探索了操纵IGF-I系统来预防这种情况的方法，并建立在研究小组开发的一些技术的基础上，这些技术已经被证明在控制牛皮癣方面是有效的。该项目还承诺发现尚未发现的生长调节剂，可以用于治疗皮肤过度生长疾病的新基因疗法。

Our skin protects us from damage, dehydration, infection and harmful UV radiation. At the same time, we expect it to remain healthy, smooth and looking good. How the skin, and more particularly its upper layer, the epidermis, adapts to all these requirements is a complex problem yet to be fully understood. This question forms the basis of our project proposal. The epidermis is a continuously self-renewing tissue, in which cells have an average life of 30 days before they are invisibly shed to the outside. In normal states and when responding to injury or disease, this cell turnover speed can be finely tuned, for example accelerated in the case of a healing wound. In contrast, if damaged by the sun, epidermal cells undergo a form of cell suicide (apoptosis) to prevent tumours forming from cells with damaged genes. This changing turnover speed is controlled by a series of growth factors, or cytokines. Insulin-like growth factor-I (IGF-I) is a unique cytokine that can control both cell turnover rate, and cell death. We aim to uncover the complex biochemical interactions that allow the epidermal IGF-I system to achieve this seemingly contradictory task. This study is important because when the epidermis loses the ability to finely tune its turnover speed, ulcers, sun damage, the common skin disorder psoriasis, or worse still, skin tumours, arise. This project explores ways of manipulating the IGF-I system to prevent this, and builds on some technology developed by the research group that has already proven effective in the control of psoriasis. The project also promises to discover undiscovered growth regulators that could be used in new gene therapies for skin overgrowth diseases.