Skin-Expressing lncRNAs in Inflammatory Responses.
Skin-Expressing lncRNAs in Inflammatory Responses.
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DOI：
10.3389/fgene.2022.835740
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发表时间：
2022
影响因子：
3.7
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中科院分区：
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长链非编码RNA（lncRNAs）因其在调节角质形成细胞分化和炎症反应中的潜在作用而受到关注；然而，对于许多已鉴定的在皮肤中表达的lncRNAs，其生物学作用尚未得到全面的表征。此外，由于lncRNAs的低表达特性，所报道的其表达谱可能不明确。本综述的目的是利用大规模基因组数据来表征显著在皮肤中表达的lncRNAs，旨在通过整合体外和体内数据，为它们在银屑病和特应性皮炎的炎症性皮肤病理中的潜在作用提供更多见解。我们强调了不同的在皮肤中表达的lncRNAs，包括H19，它在特应性皮炎/银屑病的皮损皮肤以及角质形成细胞受到细胞因子刺激时显著下调；它还与CYP1A1呈负相关（r = -0.75，p = 8×10⁻⁷³），CYP1A1是一个参与药物代谢和皮肤屏障稳态的基因，存在于角质形成细胞中。此外，SPRR2C是一种调节IL - 22刺激的潜在调节因子，在特应性皮炎和银屑病皮损皮肤中均上调，并且也是角质形成细胞中IL - 17A和IL - 17 + TNF信号通路的下游靶点。通过单细胞RNA测序，我们进一步揭示了lncRNAs的细胞类型特异性，包括H19在表皮中的基底细胞表达特性。有趣的是，我们发现少数lncRNAs在皮肤的不同细胞类型中均有表达，而非具有细胞类型特异性表达谱，这些lncRNAs包括MALAT1、NEAT1和GAS5。虽然lncRNAs通常表达较低，但我们结合体外和体内实验数据的结果表明，其中一些lncRNAs如何在细胞因子刺激的通路中发挥介导作用。
Long non-coding RNAs (lncRNAs) have attracted attention for their potential roles in modulating keratinocyte differentiation and inflammatory response; however, for many identified skin-expressing lncRNAs, there is no comprehensive characterization regarding their biological roles. In addition, the reported expression profiles for lncRNAs can be ambiguous due to their low-expressing nature. The objective of this review is to utilize large scale genomic data to characterize the prominent skin-expressing lncRNAs, aiming to provide additional insights for their potential roles in the pathology of inflammatory skin of psoriasis and atopic dermatitis by integrating in vitro and in vivo data. We highlighted the different skin-expressing lncRNAs, including H19, which is significantly down-regulated in lesional skin of AD/psoriasis and upon cytokine stimulation in keratinocytes; it is also negatively correlated with CYP1A1 (r = -0.75, p = 8 × 10−73), a gene involved in drug metabolism and skin barrier homeostasis, in keratinocytes. In addition, SPRR2C, a potential regulator that modulates IL-22 stimulation, was upregulated in both atopic dermatitis and psoriasis lesional skin and was also downstream of the IL-17A and IL-17 + TNF signaling in keratinocytes. Using scRNAseq, we further revealed the cell type specificity of lncRNAs, including basal-expressing nature of H19 in the epidermis. Interestingly, instead of having cell type specific expression profile, we found few lncRNAs that are express across different cell types in skin, including MALAT1, NEAT1, and GAS5. While lncRNAs in general have lower expression, our results combining in vitro and in vivo experimental data demonstrate how some of these lncRNAs can play mediator roles in the cytokine-stimulated pathway.