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Skin-Expressing lncRNAs in Inflammatory Responses
Alanna Shefler1, Matthew T Patrick1, Rachael Wasikowski1
1Department of Dermatology, University of Michigan Medical School, Ann Arbor, MI, United States.
Frontiers in Genetics
|May 13, 2022
Summary
Long non-coding RNAs (lncRNAs) are key in skin inflammation. This study characterizes skin lncRNAs, revealing their roles in psoriasis and atopic dermatitis by integrating in vitro and in vivo data.
Area of Science:
- Dermatology and Molecular Biology
- Investigates the role of long non-coding RNAs (lncRNAs) in skin biology and inflammatory diseases.
Background:
- Long non-coding RNAs (lncRNAs) are implicated in keratinocyte differentiation and inflammation, but their specific roles in skin are not fully understood.
- Expression profiles of lncRNAs are often ambiguous due to low expression levels.
- Understanding lncRNA function is crucial for inflammatory skin conditions like psoriasis and atopic dermatitis (AD).
Purpose of the Study:
- To characterize prominent skin-expressing lncRNAs using large-scale genomic data.
- To provide insights into the potential roles of these lncRNAs in the pathology of psoriasis and atopic dermatitis.
- To integrate in vitro and in vivo data for a comprehensive understanding of lncRNA function in skin.
Main Methods:
- Analysis of large-scale genomic data to identify and characterize skin-expressing lncRNAs.
- Integration of in vitro (keratinocyte cell cultures) and in vivo (lesional skin samples) experimental data.
- Utilized single-cell RNA sequencing (scRNAseq) to determine cell type specificity of lncRNA expression.
- Correlation analysis between lncRNA expression and specific genes (e.g., H19 and CYP1A1).
Main Results:
- Identified key skin-expressing lncRNAs, including H19, which is downregulated in lesional skin of AD/psoriasis and negatively correlated with CYP1A1.
- SPRR2C was upregulated in lesional skin of AD and psoriasis and found to be downstream of IL-17A and IL-17 + TNF signaling.
- scRNAseq revealed cell type-specific expression for some lncRNAs (e.g., H19 in basal epidermis), while others like MALAT1, NEAT1, and GAS5 showed broader expression.
- Demonstrated that certain lncRNAs can act as mediators in cytokine-stimulated pathways despite generally low expression levels.
Conclusions:
- Characterized prominent skin-expressing lncRNAs, highlighting their differential expression in inflammatory skin diseases.
- lncRNAs such as H19 and SPRR2C play significant roles in the pathogenesis of psoriasis and atopic dermatitis.
- lncRNAs can mediate inflammatory responses in skin cells, offering potential therapeutic targets.
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