The Role of MicroRNAs in Epidermal Barrier

Abstract

MicroRNAs (miRNAs), which mostly cause target gene silencing via transcriptional repression and degradation of target mRNAs, regulate a plethora of cellular activities, such as cell growth, differentiation, development, and apoptosis. In the case of skin keratinocytes, the role of miRNA in epidermal barrier integrity has been identified. Based on the impact of key genetic and environmental factors on the integrity and maintenance of skin barrier, the association of miRNAs within epidermal cell differentiation and proliferation, cell–cell adhesion, and skin lipids is reviewed. The critical role of miRNAs in the epidermal barrier extends the use of miRNAs for control of relevant skin diseases such as atopic dermatitis, ichthyoses, and psoriasis via miRNA-based technologies. Most of the relevant miRNAs have been associated with keratinocyte differentiation and proliferation. Few studies have investigated the association of miRNAs with structural proteins of corneocytes and cornified envelopes, cell–cell adhesion, and skin lipids. Further studies investigating the association between regulatory and structural components of epidermal barrier and miRNAs are needed to elucidate the role of miRNAs in epidermal barrier integrity and their clinical implications.

The Balance between Differentiation and Terminal Differentiation Maintains Oral Epithelial Homeostasis

“…In mammalian epidermis, it was shown that the Grainy-head like 3 (GRHL3), an evolutionarily conserved transcription factor and a master regulator of terminal keratinocyte differentiation [66,67], is repressed by oncogenic miR-21 [68,69]. Importantly, an epidermal-specific loss of key miRNA processing machinery components, such as Dicer and Dgcr8, causes epidermal dehydration, hair follicle apoptosis and neonatal lethality [70]. These results underscore the importance of regulating protein expression associated with differentiation and invite further investigations of the multi-level controls of this process.…”

Maximizing the Utility of Transcriptomics Data in Inflammatory Skin Diseases

“…This might be due to the maintenance of skin barrier function largely relies on homeostatic conditions between cellular motility and excessive tissue destruction. Kallikrein-related peptidase (KLK) genes, such as KLK5, KLK14, and lipid metabolism gene ELOVL1, were downregulated in AD skin (29), while protease inhibitor SPINK5 (serine protease inhibitor of kazal type 5) and human aquaporin 3 (AQP3) were up-regulated, which function in elevating inflammatory responses and epidermal water loss, respectively (29,91).…”

Epigenetic Regulation of Epidermal Differentiation

“…Regarding keratinocyte differentiation, several studies documented the pattern of changes in miRNA expression during the course of human keratinocyte differentiation in vitro and in vivo [ 34 , 35 , 36 ]. There is a number of reports documenting, through both knockout/knockdown and overexpression of individual miRNAs, their role in epidermal development and differentiation.…”

“…As indicated earlier, p63 is a transcription factor that maintains the proliferative potential of epidermal stem cells, while Notch signaling promotes keratinocyte differentiation [ 38 ]. Although miR-184 was shown not to target p63 directly, there are other miRNAs that regulate p63 level, among them miR-203, whose expression is inversely correlated with that of p63 along the path of keratinocyte differentiation [ 36 , 39 ]. Another miRNA, miR-214, was shown to target β-catenin and cause lower activity of the Wnt pathway [ 32 ].…”