In the pathogenesis of dermal inflammation, sebaceous glands (SGs) were considered as impotent players that are under the control of other cell types, but without any feedback on them. Only research of the past decade put SGs into our focus showing that besides their contribution to the lipid layer covering the skin surface and the hair, SGs are also capable of exerting inflammatory responses, thus providing an interesting cell type where lipid metabolism and inflammation is linked at a cellular level.
The genetic programs responsible for the dual functions of lipid metabolism and inflammation in SGs can be regulated at various levels. Members of the DNA binding nuclear receptor superfamily such as vitamin D or the vitamin A receptors, the master regulators that sense the lipid environment and regulate different cellular functions via the regulation of their target genes, are expressed also in SGs although their cell specific effect on the gene expression was approached in only a limited extent. Recently, microRNAs, short non-coding RNAs that negatively regulate gene expression by binding to their specific target mRNA(s), representing another level of gene expression regulation, were also shown to be expressed in SGs, however, their function in SGs of skin diseases/skin inflammation is as yet unexplored.
In the proposed study we aim to identify and link the genetic programs and their possible regulators in SGs that lead to their dual function of active lipid metabolism and inflammation. Furthermore, putting and comparing SGs in different disease specific contexts of inflammation such as acne and atopic dermatitis provides interesting models for dermatological research that may open many new avenues for understanding the role of SGs in disease progression and in the development of new therapies.
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