银屑病相关miRNAs表达的研究进展

微RNA(miRNAs)是一种大小约18~25个核苷酸的非编码小分子RNA,具有调控基因表达的作用,参与细胞增殖、分化、凋亡、发育等多种生物学过程,是疾病发生的总"开关"。近年来研究发现多种miRNA在银屑病皮损组织和血浆中有异常表达,是银屑病发生、发展过程中重要的调控因素。本文就这些特异性miRNAs与银屑病发病机制的关系以及在银屑病早期诊断和治疗中的应用做一综述。     

银屑病相关 miRNAs 表达的研究进展

微RNA（miRNAs）是一种大小约18～25个核苷酸的非编码小分子 RNA,具有调控基因表达的作用,参与细胞增殖、分化、凋亡、发育等多种生物学过程,是疾病发生的总“开关”。近年来研究发现多种miRNA在银屑病皮损组织和血浆中有异常表达,是银屑病发生、发展过程中重要的调控因素。本文就这些特异性miRNAs与银屑病发病机制的关系以及在银屑病早期诊断和治疗中的应用做一综述。     

MiRNAs、易感基因及细胞因子系统生物学网络在银屑病发病机制的研究进展

银屑病(Psoriasis,PS)是一种遗传和环境共同作用,以角质形成细胞过度增殖为特征,由免疫介导的慢性炎症性皮肤病。银屑病病理过程中,调控基因表达的小分子RNA(miRNAs)、易感基因以及细胞因子,三者之间有着重要的关联。之前的研究往往集中三者其中的某一方面,这样并不能够良好地理解其完整病理过程。本综述从系统生物学(Systems biology)的整体角度,整合前期研究者的数据信息,探讨miRNAs、易感基因、细胞因子在银屑病发病机制之间的关联以及相互调控作用。本文综述miRNAs、易感基因以及细胞因子生物网络在PS病理过程的进展,为银屑病病理机制提供一个全新视角。     

寻常型银屑病患者外周血中 miRNAs 表达的研究

目的：探讨微小RNA（ miRNAs）在寻常型银屑病患者血浆中的表达及临床意义。方法：用基因芯片技术筛选银屑病患者和正常人血浆中差异性表达的 miRNA,并通过生物信息学对差异表达的miRNA进行靶基因预测及靶基因功能富集分析。结果：寻常型银屑病患者血浆中实验组和对照组相比,当P＜0.05,FC＞1.5时,血浆中差异miRNA共22个,其中17个表达上调,5个表达下调。结论：银屑病血浆中存在着表达差异的miRNA,这些差异表达的 miRNA可能在银屑病的发病机制中占有重要的地位。     

银屑病与非酒精性脂肪性肝病相关性研究进展

研究报道银屑病和非酒精性脂肪性肝病（NAFLD）的发病机制中有共同参与的炎症及细胞因子，银屑病可增加NAFLD的发病风险。胰岛素抵抗、TNF-α及脂肪因子已被证实在银屑病合并NAFLD的发病中具有重要作用。本文对银屑病与非酒精性脂肪性肝病相关性研究进展进行了综述。     

银屑病的动物模型与细胞模型研究进展

 银屑病的发病机制很复杂，目前尚未完全阐明。银屑病主要特征是表皮过度增生和明显的炎症浸润。在人类银屑病中观察到的特征也可在各种银屑病动物模型及体外模型中观察到，这些模型已广泛应用于银屑病的组织病理学、发病机制和对药物反应等研究。目前用于银屑病研究的模型主要包括动物模型和细胞模型，其中常用的动物模型有自发模型、转基因动物模型、药物诱导的模型（局部皮肤外用咪喹莫特）以及异体移植模型。这些模型虽然不能完全精确重现人类银屑病的发生及发展过程，但在揭示其可能的发病机制、新药测试等方面有重要价值。本文就银屑病的动物模型与细胞模型研究进展作一综述。     

Oxidative stress and psoriasis

银屑病是一种常见的慢性炎症性皮肤病,尽管对其病因及发病机制进行了大量研究,但具体机制仍未完全阐明.目前,氧化应激在银屑病中的作用受到关注.该文从银屑病中存在氧化应激、氧化应激参与银屑病的发病机制、银屑病治疗与抗氧化应激三方面进行综述.     

银屑病患者来源干细胞在其发病中的作用

银屑病是一种由免疫介导的慢性、复发性、炎症性、系统性疾病，目前尚无根治手段。干细胞是一类能够分化为多种组织和器官的多能细胞，具有低免疫原性、免疫调节和抗炎等特性，在体内具有迁移性和旁分泌作用。众多学者聚焦于干细胞治疗银屑病的潜能，开展了系列的基础研究和临床试验，极大地推动了干细胞应用于银屑病治疗的进程。另一方面，研究者们逐渐发现银屑病患者自身来源干细胞在其发病中发挥着重要作用，对该领域的深入研究有助于丰富银屑病的发病机制。本文对银屑病患者来源干细胞在其发病中的作用进行综述，为干细胞在银屑病发病中的机制研究提供了一定思路。     

银屑病发病易感基因与表观遗传调控研究进展

银屑病是一种常见的慢性炎症性皮肤病，它是一种复杂的多因素性疾病，确切发病机制尚不明确，位于主要组织相容性复合体区域染色体6p21.3上的主要效应基因所起的遗传效应只占银屑病遗传可能性的三分之一，因此这不能完全解释银屑病的发病机制。研究发现，表观遗传学机制也参与银屑病的发病，如DNA甲基化、乙酰化修饰和MicroRNA调节。本文对银屑病发病易感基因及表观遗传调控进展进行综述。     

银屑病动物模型

银屑病罕见于任何非人类动物,且自然出现的病例极其少见,不适于进行科学研究,所以,银屑病动物模型的建立显得尤为必要。各个时期建立的银屑病动物模型依赖于对银屑病的认识水平和其它相关学科的发展,所以,随着对银屑病发病机制研究的深入和研究技术的逐步提高所建立的动物模型也越来越多,越来越能反映银屑病实际发病状况。这些模型中有些是以构建银屑病动物模型为直接研究目的建立起来的,而有些则是在银屑病发病机制及治疗研究过程中偶然发现的。每一种模型的建立均给银屑病发病机制及治疗研究提供了受试主体,并对银屑病的研究产生了积极的…     

MiR-125b, a microRNA downregulated in psoriasis, modulates keratinocyte proliferation by targeting FGFR2

MicroRNAs (miRNAs) are short, single-stranded, noncoding RNAs that play important roles in the regulation of gene expression. We previously identified a characteristic miRNA expression profile in psoriasis, distinct from that of healthy skin. One of the most downregulated miRNAs in psoriasis skin was microRNA-125b (miR-125b). In this study, we aimed to identify the potential role(s) of miR-125b in psoriasis pathogenesis. In situ hybridization results showed that the major cell type responsible for decreased miR-125b levels in psoriasis lesions was the keratinocyte. Overexpression of miR-125b in primary human keratinocytes suppressed proliferation and induced the expression of several known differentiation markers. Conversely, inhibition of endogenous miR-125b promoted cell proliferation and delayed differentiation. Fibroblast growth factor receptor 2 (FGFR2) was identified as one of the direct targets for suppression by miR-125b by luciferase reporter assay. The expression of miR-125b and FGFR2 was inversely correlated in both transfected keratinocytes and in psoriatic skin. Knocking down FGFR2 expression by siRNA suppressed keratinocyte proliferation, but did not enhance differentiation. Altogether, our results demonstrate a role for miR-125b in the regulation of keratinocyte proliferation and differentiation, partially through the regulation of FGFR2. Loss of miR-125b in psoriasis skin may contribute to hyperproliferation and aberrant differentiation of keratinocytes.     

Genetic polymorphisms altering microRNA activity in psoriasis – a key to solve the puzzle of missing heritability?

Psoriasis is a chronic immune‐mediated skin disease in which the balance in the interplay of immune cells and keratinocytes is disturbed. MicroRNAs (miRNAs) are endogenous small regulatory RNAs that stabilize cellular phenotypes and fine‐tune signal transduction feedback loops through the regulation of gene networks. Through the regulation of their multiple target genes, miRNAs regulate the development of inflammatory cell subsets and have a significant impact on the magnitude of inflammatory responses. Since the discovery of deregulated miRNA expression in psoriasis, we have learned that they can regulate differentiation, proliferation and cytokine response of keratinocytes, activation and survival of T cells and the crosstalk between immunocytes and keratinocytes through the regulation of chemokine production. In recent years, it became apparent that genetic polymorphisms in miRNA genes and/or in miRNA binding sites of target genes can affect miRNA activity and contribute to disease susceptibility. Psoriasis has a strong genetic background; however, the contribution of genetic variants involving miRNAs is largely unexplored in psoriasis. We propose that changes in miRNA‐mediated gene regulation may be a major contributor to the disturbed balance in immune regulation that results in chronic skin inflammation. In this viewpoint essay, we focus on the emerging new aspects of the role of miRNAs in psoriasis and propose that genetic polymorphisms that affect miRNA activity might be important in the pathogenesis of psoriasis.     

MicroRNAs与慢性炎症性皮肤病

MicroRNAs是一类非编码的单链小分子RNA,对于多细胞器官的发育和存活来说是非常关键的。目前已经发现明确与银屑病和特应性皮炎发病相关的miRNAs有miR-203,miR-146a,miR-21,miR-125b。miR-203是第一个被发现的皮肤特异性miRNA,它在皮肤角质形成细胞中有表达,在银屑病皮损的角质形成细胞中表达最为明显。miR-146a在银屑病中具有特异的上调作用,它能够调控天然免疫反应和肿瘤坏死因子通路。miR-125b亦参与肿瘤坏死因子通路,但对银屑病和特应性皮炎的病情发展具有负向调控作用。     

微小RNA在皮肤疾病中的调控作用研究进展

摘要：MicroRNAs是近年来发现的一类由19-25个核苷酸组成的非编码单链小RNA分子,它们通过与靶基因3’UTR结合抑制靶基因的翻译,在转录后水平调控基因表达。miRNA参与了包括细胞分化、增殖和凋亡及免疫系统应答在内的一系列发育调控和生物学过程。最近研究发现MicroRNAs在许多皮肤疾病的发病机制中都发挥了重要的调控作用。本文综述了近几年来MicroRNAs在皮肤肿瘤、银屑病、自身免疫病-系统性红斑狼疮和全身硬皮病、男性斑秃及创伤愈合等多种皮肤疾病中的研究进展,为皮肤疾病的诊断和治疗提供了新的方向和可能性。     

银屑病发病机制中免疫学研究进展

银屑病的发病机制与免疫关系密切,近几年研究倾向于银屑病是Th1/Th17混合途径的免疫性疾病.银屑病的发病中除了有树突细胞、T细胞、角质形成细胞以及Tb1型的细胞因子如白介素12、白介素18等参与外,还有Th17型细胞因子,如白介素23及白介素22等的参与,Th17型免疫反应可能在银屑病发病中起到重要的作用.     

银屑病代谢组学研究进展

银屑病是临床常见的复发难治性皮肤病,其精准诊疗是皮肤科领域研究的热点。代谢组学广泛运用于疾病机制、药效评价等研究领域。本文综述近年来国内外基于代谢组学技术开展银屑病代谢标志物筛选、代谢通路分析与网络构建、药物代谢效应靶标等进展,并就当前存在的问题进行归纳和展望,以期为研究其发病机制,进而实现精准治疗提供参考。     

The roles of cells and cytokines in the pathogenesis of psoriasis

Psoriasis is considered an immune chronic disease in which T cells are accepted as important. Nowadays, it is believed that psoriasis is most likely a T helper (Th)1/Th17 induced inflammatory disease. However, some other cells, such as endothelial cells, dendritic cells, monocytic cells, neutrophils, keratinocytes, and several cytokines, appear to have, at different stages of the disease, an important role in its pathogenesis. For instance, the response to psoriasis therapy is dependent not only on the inactivation of Th1 and Th17 immune responses but also on the inactivation of dendritic cell products. Moreover, interleukin (IL)-23 deregulation appears to be an independent factor in the pathogenesis of psoriasis. Indeed, currently, the IL-23/Th17 axis is believed to be crucial in psoriasis pathogenesis, and its inhibition appears to be important for therapeutic achievement. This review presents the roles and interactions of cells and cytokines that are related to psoriasis pathogenesis.     

A comprehensive review of biomarkers in psoriasis

Psoriasis is a common, chronic skin disorder, the pathogenesis of which is incompletely understood. Results from various clinical and experimental studies indicate that psoriasis is a complex, multifactorial disease with a genetic predisposition. Factors such as climate, physical trauma, drug, stress and infections ( Streptococcus , human immunodeficiency virus) are known to trigger psoriasis. The success of treatment of psoriasis with T-cell depletion and antitumour necrosis factor (TNF)-α treatment is explained by the involvement of T cells and TNF- α in the pathogenesis of psoriasis. The biochemical basis for the pathogenesis of psoriasis can be attributed to both overexpression and underexpression of certain proteins in psoriatic lesions. The anomalies in protein expression can be classified as abnormal keratinocyte differentiation, keratinocyte hyperproliferation and inflammation. Oxidative stress (OS) and increased free-radical generation have been linked to skin inflammation in psoriasis. The review presents evidence for various markers of psoriasis that can be targeted for effective treatment, including biomarkers of inflammation, keratinocyte hyperproliferation and abnormal differentiation, and stress.     

Psoriasis in the patient with human immunodeficiency virus, part 1: review of pathogenesis

Psoriasis is a chronic, immune-mediated skin disease affecting approximately 1% to 3% of the human immunodeficiency virus (HIV)-infected population. The presentation of psoriasis in patients with HIV varies. It either presents as the first clinical manifestation of HIV or, less commonly, appears in the advanced stages of HIV when it has progressed to AIDS. This 2-part series reviews the pathogenesis of HIV-associated psoriasis as well as the various therapeutic regimens that have effectively treated psoriasis in patients with HIV These therapies address the profound immune dysregulation that defines psoriasis. The first part of the series focuses on the pathogenesis of HIV-associated psoriasis.