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环境、表观遗传机制和非编码RNA在银屑病中的作用

Contribution of the Environment, Epigenetic Mechanisms and Non-Coding RNAs in Psoriasis.

作者信息

Antonatos Charalabos, Grafanaki Katerina, Asmenoudi Paschalia, Xiropotamos Panagiotis, Nani Paraskevi, Georgakilas Georgios K, Georgiou Sophia, Vasilopoulos Yiannis

机构信息

Laboratory of Genetics, Section of Genetics, Cell Biology and Development, Department of Biology, University of Patras, 26504 Patras, Greece.

Department of Dermatology, School of Medicine, University Hospital of Patras, University of Patras, 26504 Patras, Greece.

出版信息

Biomedicines. 2022 Aug 9;10(8):1934. doi: 10.3390/biomedicines10081934.

Abstract

Despite the increasing research and clinical interest in the predisposition of psoriasis, a chronic inflammatory skin disease, the multitude of genetic and environmental factors involved in its pathogenesis remain unclear. This complexity is further exacerbated by the several cell types that are implicated in Psoriasis's progression, including keratinocytes, melanocytes and various immune cell types. The observed interactions between the genetic substrate and the environment lead to epigenetic alterations that directly or indirectly affect gene expression. Changes in DNA methylation and histone modifications that alter DNA-binding site accessibility, as well as non-coding RNAs implicated in the post-transcriptional regulation, are mechanisms of gene transcriptional activity modification and therefore affect the pathways involved in the pathogenesis of Psoriasis. In this review, we summarize the research conducted on the environmental factors contributing to the disease onset, epigenetic modifications and non-coding RNAs exhibiting deregulation in Psoriasis, and we further categorize them based on the under-study cell types. We also assess the recent literature considering therapeutic applications targeting molecules that compromise the epigenome, as a way to suppress the inflammatory cutaneous cascade.

摘要

尽管对银屑病(一种慢性炎症性皮肤病)的易感性研究和临床关注度不断提高,但其发病机制中涉及的众多遗传和环境因素仍不明确。银屑病进展过程中涉及多种细胞类型,包括角质形成细胞、黑素细胞和各种免疫细胞类型,这进一步加剧了这种复杂性。遗传底物与环境之间观察到的相互作用导致表观遗传改变,直接或间接影响基因表达。DNA甲基化和组蛋白修饰的变化会改变DNA结合位点的可及性,以及参与转录后调控的非编码RNA,这些都是基因转录活性修饰的机制,因此会影响银屑病发病机制中涉及的途径。在这篇综述中,我们总结了关于导致疾病发生的环境因素、银屑病中表现出失调的表观遗传修饰和非编码RNA的研究,并根据正在研究的细胞类型对它们进行了进一步分类。我们还评估了最近的文献,这些文献考虑了针对影响表观基因组的分子的治疗应用,以此作为抑制皮肤炎症级联反应的一种方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c282/9405550/4ba52dfa63a8/biomedicines-10-01934-g001.jpg

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