On the Role of the Epidermal Differentiation Complex in Ichthyosis Vulgaris, Atopic Dermatitis and Psoriasis

S. Hoffjan; S. Stemmler

Disclosures

The British Journal of Dermatology. 2007;157(3):441-449. 

In This Article

The Epidermal Differentiation Complex on Chromosome 1q21

On human chromosome 1q21, a region spanning approximately 2 Mb was described that contains a number of genes which fulfill important functions in epidermal differentiation.[8] This chromosomal region was named the EDC (Fig. 2). To date, at least 45 genes have been identified within the EDC. Several of these genes code for proteins involved in the formation of the cornified envelope, including loricrin, involucrin and SPRRs. Other genes encode calcium-binding proteins of the S100A family, late cornified envelope (LCE) proteins and the multifunctional proteins (pro)filaggrin and trichohyalin.[8]

Loricrin and involucrin are major components of the cornified envelope.[9] Mutations within the loricrin gene were found to cause a variant form of Vohwinkel syndrome,[10] a rare genetic disorder characterized by disturbed cornification. The SPRRs show strong sequence homology to loricrin and involucrin proteins.[11] To date, 17 different SPRRs are known, which are divided into three subfamilies (SPRR1, SPRR2 and SPRR3). In addition to their function as structural proteins it has been suggested that they might also be involved in gene regulation, possibly in limiting proliferation and promoting differentiation.[12] Increased expression of SPRR1 and SPRR2 was measured in orthokeratotic and parakeratotic hyperkeratosis (e.g. in psoriasis vulgaris and lichen planus), whereas in differentiating epidermal tumours the expression of SPRR3 was increased.[13]

S100A proteins are calcium-activated signal proteins characterized by a low molecular weight and the presence of two calcium-binding EF-hand motifs. Fifteen of the S100A proteins (S100A1-S100A14, S100A16) are located within the EDC.[14,15] The expression of some S100A proteins (e.g. S100A2, A7, A8, A9, A15) is increased in different skin diseases, for example, cancer, psoriasis or inflammation of the skin.[14] Furthermore, upregulation of S100A8 and S100A9 has been implicated in wound repair.[16]

Eighteen different LCE genes are located within a subcluster of the EDC. They also show strong sequence homology to the above-mentioned proteins. These genes are expressed very late during epidermal differentiation.[17] (Pro)filaggrin and trichohyalin are multifunctional proteins known to play an important role during cornification (see above). The genes encoding these two proteins are characterized by multiple tandem repeats of specific peptide motifs and are thought to result from a fusion of cornified envelope proteins and genes of the S100 family.[18]

In conclusion, the EDC represents a remarkable cluster of structurally and evolutionarily related genes that closely cooperate in the complex mechanism of epidermal differentiation.

Figure 2.

Structure of the epidermal differentiation complex (EDC). The EDC is a gene cluster on chromosome 1q21 which houses a collection of genes and gene familiesinvolved in epidermal differentiation. These include loricrin, involucrin, filaggrin, the S100 gene family, the late cornified envelope (LCE) gene family and the small proline-rich proteins (SPRRs). Source: UCSC Genome Browser database (http://genome.ucsc.edu/).

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