AUTHOR=Wang Jiating , Huang Yejing , Wu Xinfeng , Li Dongqing 

TITLE=MicroRNA-939 amplifies Staphylococcus aureus-induced matrix metalloproteinase expression in atopic dermatitis

JOURNAL=Frontiers in Immunology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1354154

DOI=10.3389/fimmu.2024.1354154

ISSN=1664-3224

ABSTRACT=<sec><title>Background</title><p>Atopic dermatitis (AD) is a common chronic inflammatory skin diseases that seriously affects life quality of the patients. <italic>Staphylococcus aureus</italic> (<italic>S. aureus</italic>) colonization on the skin plays an important role in the pathogenesis of AD; however, the mechanism of how it modulates skin immunity to exacerbate AD remains unclear. MicroRNAs are short non-coding RNAs that act as post-transcriptional regulators of genes. They are involved in the pathogenesis of various inflammatory skin diseases.</p></sec><sec><title>Methods</title><p>In this study, we established miRNA expression profiles for keratinocytes stimulated with heat-killed <italic>S. aureus</italic> (HKSA). The expression of miR-939 in atopic dermatitis patients was analyzed by fluorescence in situ hybridization (FISH). miR-939 mimic was transfected to human primary keratinocyte to investigate its impact on the expression of matrix metalloproteinase genes (MMPs) <italic>in vitro</italic>. Subsequently, miR-939, along with Polyplus transfection reagent, was administered to MC903-induced atopic dermatitis skin to assess its function <italic>in vivo</italic>.</p></sec><sec><title>Results</title><p>MiR-939 was highly upregulated in HKSA-stimulated keratinocytes and AD lesions. <italic>In vitro</italic> studies revealed that miR-939 increased the expression of matrix metalloproteinase genes, including MMP1, MMP3, and MMP9, as well as the cell adhesion molecule ICAM1 in human primary keratinocytes. <italic>In vivo</italic> studies indicated that miR-939 increased the expression of matrix metalloproteinases to promote the colonization of <italic>S. aureus</italic> and exacerbated <italic>S. aureus</italic>-induced AD-like skin inflammation.</p></sec><sec><title>Conclusions</title><p>Our work reveals miR-939 is an important regulator of skin inflammation in AD that could be used as a potential therapeutic target for AD.</p></sec>