IL‐4 dysregulates microRNAs involved in inflammation, angiogenesis and apoptosis in epidermal keratinocytes

Abstract

IL-4 plays an important role in the pathogenesis of atopic dermatitis (AD) by dysregulating many key factors at the transcriptional level. In this study, a microRNA array technique and IL-4 transgenic mice were used to demonstrate that IL-4 dysregulates microRNAs involved in inflammation, angiogenesis, lymphangiogenesis and apoptosis. Of the 372 common microRNAs examined, 26 and one microRNAs were found to be up-and down-regulated, respectively. MicroRNA-101-5p, À122-5p, À142-3p, À204-5p, À335-3p, À376a-3p, À378a-5p, À639 and À9-5p are among the most significantly up-regulated microRNAs. MicroRN A-147a, the only one that was down-regulated in the present study, attenuates TLR-induced inflammatory responses. These dysregulated microRNAs may provide post-transcriptional regulation of key genes in AD.

Cutaneous microRNA expression in healthy Labrador and Golden retrievers and retrievers with allergic and inflammatory skin diseases

“…40 Increased expression of miR-142 was detected in IL-4 transfected human keratinocytes and a mouse model of human AD, revealing keratinocytes as one possible source of miR-142 expression. 42 In one study examining the effect of miR-142 on human and murine mast cells, an enhanced high-affinity immunoglobulin (Ig)E receptor FceRI-mediated degranulation activity in transfected cells was identified, outlining a possible mechanism by which miR-142 can contribute to ongoing inflammation. 43 Expression of miR-146, as miR-142, was upregulated not only in allergic dogs in this study, but also in the skin of human patients with AD, as well as in psoriatic lesions.…”

“…28 Elevated expression in human AD patients can be found mainly in infiltrating immune cells, such as CD4+ Th cells and dendritic cells, yet fibroblasts, mast cells and human keratinocytes also are capable of expressing miR-155. 28,29,42 Suppressor of cytokine signalling (SOCS) 1, a negative regulator of the JAK/STAT (Signal Transducer and Activator of Transcription) signalling pathway, is another direct target of miR-155. By inhibiting SOCS1, miR-155 influences the regulation of activation, differentiation and function of lymphocytes mediated by the JAK/ STAT pathway.…”

Genetics and Epigenetics of Atopic Dermatitis: An Updated Systematic Review

“…As a result, 73 articles were evaluated. Out of 73 studies, 11 were related to epigenetics [13,[24][25][26][27][28][29][30][31][32][33], 39 were candidate gene studies , 5 were genome-wide association studies (GWAS) [5,13,[74][75][76], whole-exome sequencing (WES) was performed in 7 articles [77][78][79][80][81][82][83], and phenome-wide association sequencing was done in 1 article [84]. Four studies described results from next-generation sequencing (NGS) [85][86][87][88], and 2 showed analyses of copy number variations (CNV) [89,90].…”

“…After comparing lesional skins samples with non-lesional skin samples in AD patients, Ding et al proposed a regulatory network of differentially expressed genes that included 182 miRNAs, and among them, hsa-miR-148b, hsa-miR-152, and hsa-miR-324 [24]. Finally, using primary adult human keratocytes, several out of the 372 most common miRNAs were dysregulated when exposed to IL-4, which plays a key role in the development of AD [27].…”

“…Thus, downregulation of miR-124 in AD lesions has been shown to control NF-κB-dependent inflammatory responses in keratinocytes and chronic skin inflammation in atopic eczema [25]. Bioinformatics analyses from two studies suggest that miRNAs can influence the transcriptional regulation of signalling pathways related to the synthesis of extracellular matrix components, such as arachidonic acid and hyaluronic acid, as well as participate in processes such angiogenesis, lymphangiogenesis and apoptosis, all of which are involved in AD progression [24,27].…”