Diseases like atopic dermatitis or skin cancer could benefit from these results.
The formation of human skin involves a cascade of yet well known biochemical signals, but very important since their failures cause diseases that affect more than a quarter of humanity from atopic dermatitis to cancers of skin. Now a team of researchers from the National Cancer Research Centre have gone a step further to reveal this process discovering one of the key links, a new mechanism that regulates the differentiation of the cells that make up most of the epidermis, keratinocytes. They have reported that this mechanism could be involved in skin cancer.
The authors, whose work is published in “Genes & Development”, has identified Fra-2 protein whose precise function in the skin until now was unknown as a key element in the differentiation of keratinocytes.
Human keratinocytes live about a month, and in that period go through a series of related to the different functions performed during its journey from the deepest layer of the epidermis, where they are born until the surface changes with which our body playing outside. This evolution is called keratinocyte differentiation. The induction of keratinocyte differentiation is essential for the acquisition of the barrier function of the skin, and for fabric stability.
In recent years it has been unraveling many biochemical signals involved in the transformation of keratinocytes and therefore in the formation of the epidermis. Today we know that the process is run by a plethora of localized in Epidermal Differentiation Complex call (EDC) genes. In turn, the expression of these genes is regulated by the coordinated interaction of biochemical signals sent by small proteins, such as transcription factors.
Fra-2, one of these transcription factors, plays a key regulatory role. Specific mouse models showed that the expression of Fra-2 in keratinocytes also induce the expression of genes in the EDC. Conversely, sufficient loss Fra-2 in the suprabasal keratinocytes layer to cause defects that prevent the proper functioning of the skin barrier, because it has reduced the expression of genes EDC. Even possible link to cancer was found. Fra-2 induces premature differentiation of keratinocytes carcinogenic.
This finding opens new ways to explore this switch as a general mechanism for activating transcription factors. Ezh2 may be a valuable therapeutic strategy against skin diseases related to failures in keratinocyte differentiation.