Genomic, Epigenomic, Transcriptomic, Proteomic and Metabolomic Approaches in Atopic Dermatitis

Abstract

Atopic dermatitis (AD) is a chronic inflammatory skin disease with a high prevalence in the developed countries. It is associated with atopic and non-atopic diseases, and its close correlation with atopic comorbidities has been genetically demonstrated. One of the main roles of genetic studies is to comprehend the defects of the cutaneous barrier due to filaggrin deficit and epidermal spongiosis. Recently, epigenetic studies started to analyze the influence of the environmental factors on gene expression. The epigenome is considered to be a superior second code that controls the genome, which includes alterations of the chromatin. The epigenetic changes do not alter the genetic code, however, changes in the chromatin structure could activate or inhibit the transcription process of certain genes and consequently, the translation process of the new mRNA into a polypeptide chain. In-depth analysis of the transcriptomic, metabolomic and proteomic studies allow to unravel detailed mechanisms that cause AD. The extracellular space and lipid metabolism are associated with AD that is independent of the filaggrin expression. On the other hand, around 45 proteins are considered as the principal components in the atopic skin. Moreover, genetic studies based on the disrupted cutaneous barrier can lead to the development of new treatments targeting the cutaneous barrier or cutaneous inflammation. Unfortunately, at present, there are no target therapies that focus on the epigenetic process of AD. However, in the future, miR-143 could be an important objective for new therapies, as it targets the miR-335:SOX axis, thereby restoring the miR-335 expression, and repairing the cutaneous barrier defects.

Keywords: atopic dermatitis; epigenome; genome; metabolome; proteome; transcriptome.

Figure 1

The etiology of atopic dermatitis. The complex etiology of the atopic dermatitis includes interactions between genetic predisposition, favoring and triggering factors. All these factors cause skin barrier abnormalities and immune dysfunctions critical in the pathogenesis of the disease. Adapted from Nedoszytko et al. 2020 [58].

Figure 2

From genome to metabolome. The evolution of technology allowed for a more precise analysis of the “nomes” (genome, epigenome, transcriptome, proteome, metabolome and phenome) for understanding the mechanisms that cause the AD. Genetic studies based on the disrupted cutaneous barrier lead to the development of new treatments targeting the cutaneous barrier or cutaneous inflammation. Adapted with permission from Ritchie et al. 2015 [81].

Figure 3

Skin barrier abnormalities and immune dysfunction in atopic dermatitis. The decrease in filaggrin, ceramides, antimicrobial peptides and serine protease inhibitors have a negative impact on AD, as the increase in serine proteases and the disorders of the tight junction affect the permeability of the cutaneous barrier. On the other hand, the immune dysfunction increases the risk of AD via the Th2 cells. Adapted from Yang et al. 2020 [113].