MicroRNAs: Novel Regulators Involved in the Pathogenesis of Psoriasis?

Abstract

MicroRNAs are a recently discovered class of posttranscriptional regulators of gene expression with critical functions in health and disease. Psoriasis is the most prevalent chronic inflammatory skin disease in adults, with a substantial negative impact on the patients' quality of life. Here we show for the first time that psoriasis-affected skin has a specific microRNA expression profile when compared with healthy human skin or with another chronic inflammatory skin disease, atopic eczema. Among the psoriasis-specific microRNAs, we identified leukocyte-derived microRNAs and one keratinocyte-derived microRNA, miR-203. In a panel of 21 different human organs and tissues, miR-203 showed a highly skin-specific expression profile. Among the cellular constituents of the skin, it was exclusively expressed by keratinocytes. The up-regulation of miR-203 in psoriatic plaques was concurrent with the down-regulation of an evolutionary conserved target of miR-203, suppressor of cytokine signaling 3 (SOCS-3), which is involved in inflammatory responses and keratinocyte functions. Our results suggest that microRNA deregulation is involved in the pathogenesis of psoriasis and contributes to the dysfunction of the cross talk between resident and infiltrating cells. Taken together, a new layer of regulatory mechanisms is involved in the pathogenesis of chronic inflammatory skin diseases.

miR-126 Is Downregulated in Cystic Fibrosis Airway Epithelial Cells and Regulates TOM1 Expression

“…Rodriguez et al (43) highlighted the importance of miR-155 in maintenance of a normal immune response, whereas miR-181a has a role in regulation of TCR signaling (44). Altered expression of miR-203 and miR-146 has been shown in the chronic inflammatory skin condition psoriasis, suggesting their involvement in immunemediated diseases (45). In light of our findings, it is appropriate to add miR-126 to the growing list of miRNAs with a role in finetuning innate immune responses.…”

Induction of Specific MicroRNAs Inhibits Cutaneous Wound Healing

“…1, A and B). miR-21 and -203 were previously found to be up-regulated both in psoriasis and atopic eczema (23), suggesting their possible function in hyperproliferative epidermal disorders. The striking overexpression of miR-130a and miR-21 suggests that they may play a leading role in the inhibition of wound healing.…”

“…First, for a collection of wound healing-related functional annotations (e.g., receptor growth factor, cell migration and proliferation, and transcriptional regulators), we assessed whether (i) the functional class was over-represented in the miRNA target list and (ii) the median expression change of genes in the functional class was significantly lowered in VUs (see "Experimental Procedures"). Second, we checked whether miRNA profiling evidence from other studies supported the expression of the miRNA in epithelial cells (cell line MFC10A) or in skin (21,23). Finally, we considered whether the seed class was conserved across vertebrates, because conserved miRNAs may play a more important functional role.…”

“…Specific miRNAs expressed in developing mouse epidermis and hair follicles have been identified (22). In addition, involvement of miRNAs in the pathology of psoriasis has been shown (23). A recent study has shown that hypoxia-induced miR-210 expression has an inhibiting effect on wound closure and keratinocyte proliferation in an ischemic murine wound model (24).…”

Altered expression of MicroRNA in synovial fibroblasts and synovial tissue in rheumatoid arthritis

“…It has been found that miRNA modulate T cell selection and T cell receptor sensitivity (13) as well as Treg cell development (14), which may suggest that miRNA are also involved in the development of autoimmunity. Recently, altered levels of miRNA have been linked to chronic inflammatory skin diseases (15). However, the potential role of miRNA in the pathogenesis of inflammatory and autoimmune arthritis has not yet been investigated.…”