miRNA与真菌感染免疫反应相关性的研究进展

真菌在自然界中广泛存在,人类暴露于真菌环境中可能会导致皮肤及皮下组织、呼吸系统甚至更广泛的深部真菌感染。miRNA(MicroRNA)参与调控肿瘤、心脏疾病以及感染性疾病等免疫反应,主要在转录后水平调控基因表达。最近的研究发现miRNA在真菌感染相关免疫反应中发挥着重要的作用,其能够通过调控多条分子通路来影响宿主的免疫状态,但很少有报道系统总结这些miRNA的作用及机制。该文就miRNA在真菌感染有关免疫反应中的调控作用作一综述。     

银屑病差异表达microRNA与靶基因及基因功能调控网络的研究

目的研究银屑病特异表达microRNA(miRNA)与靶基因及基因功能之间调控网络及作用机制。方法采用基因芯片技术筛选银屑病皮损组织和健康皮肤组织中差异性表达的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,构建银屑病差异表达miRNA与靶基因及基因功能调控网络,得到网络核心调控的miRNA和受调控作用的核心靶基因及关键性基因功能。结果得出银屑病皮损组织中明显上调的关键miRNA 10个,调控的关键基因12个,主要功能21项,明显下调的关键miRNA 21个,调控的关键基因22个,主要功能28项结论特异性表达的miRNA主要调控的靶基因及其基因功能与银屑病发病密切相关,为银屑病基因层面的机制研究提供了有效的依据。     

NLRP3炎症小体在银屑病发病机制中的研究进展

 NLRP3炎症小体可活化IL-1β和IL-18。近年在大量银屑病体外和体内实验中，发现NLRP3炎症小体、IL-1β和IL-18表达上升。NLRP3炎症小体参与银屑病的发病机制可能与NF-κB、P2X7、S1PR1、miRNA155等分子激活有关。阻断银屑病模型中的NLRP3炎症小体可能会影响AMPK与SIRT1分子以及T细胞信号传导通路。本文对NLRP3炎症小体与银屑病的联系、NLRP3炎症小体参与银屑病进展或调控的可能机制以及阻断NLRP3炎症小体后银屑病炎症通路的改变进行综述。     

p53调控MicroRNA与皮肤癌

p53是与人类肿瘤发生相关性最高的抑癌基因,MicroRNA是高度保守的内源性单链非编码小分子RNA。p53对MicroRNA的转录调控作用在人类肿瘤发生和发展中起着重要的作用。p53与miRNA之间的调控作用是相互的,不仅p53可以直接或间接调控多种miRNA的表达,同时多种miRNA也可以调节p53的活性和功能。p53主要转录调控分子miR-34a,miR-125b,miRNA-150,miRNA-205,miRNA-221等在某些特定的皮肤肿瘤中存在表达水平异常。随着后基因组时代的来临,miRNA在肿瘤发生发展中的作用逐渐成为国际前沿研究热点,已经证实,MicroRNA在多数肿瘤组织中存在表达异常。     

microRNA与皮肤病研究进展

miRNA(microRNA)是一类非编码RNA,长度通常为21 ～ 25个核苷酸。通过和靶mRNA的互补结合抑制蛋白表达,对机体进行多方面的调控。miRNA在多种疾病中的调控作用已得到证实,目前研究表明,miRNA和某些皮肤疾病存在一定的相关性,并在皮肤中的表达具有特征性,可以在不同种属、不同组织及不同疾病中发挥调节作用。进一步研究miRNA与皮肤疾病之间的关系也为疾病的治疗提供了新的思路及新的靶点。     

microRNA在炎症性皮肤病中作用的研究进展

【摘要】 microRNA（miRNA）是一类转录后调控基因表达的非编码RNA分子,参与皮肤各种病理生理过程。近年来,miRNA表达谱的变化已被报道与部分炎症性皮肤病相关,例如miR-203、miR-146a、miR-21在银屑病皮损中表达上调;miR-155、miR-146a在特应性皮炎皮损中表达上调;miR-21、miR-223、miR-142-3p、miR142-5p在过敏性接触性皮炎皮损表达上调;而miR-146a、miR-155在系统性红斑狼疮患者外周血表达下调;miR-223在皮肌炎皮损中表达下调等。本文综述miRNA与部分炎症性皮肤病发生、发展之间的联系。     

银屑病皮损mRNA与miRNA表达谱及网络调控分析

目的探讨银屑病患者皮损与正常皮肤组织mRNA和miRNA表达谱差异。方法利用人类基因组表达谱芯片和miRNA表达谱芯片结合基因组学和生物信息学分析银屑病皮损和正常皮肤组织差异表达的mRNA和miRNA,建立两者之间调控网络,筛选可能的核心基因。结果差异表达的mRNA 1 139个,miRNA 16个,其中3个miRNA匹配入数据库并调节168个mRNA,筛选的核心基因为IGF1、IRF1、MCL1、SERPINA1和NEK2。结论差异的miRNA调控多个mRNA参与多种生物学过程和信号通路可能促使银屑病的发生和发展。     

寻常性银屑病差异表达microRNAs与靶基因及基因功能调控网络的研究

目的:探讨寻常性银屑病差异表达microRNA(miRNA)与靶基因及基因功能之间的调控网络及作用机制。方法:采用基因芯片技术筛选寻常性银屑病患者皮损组织和血浆中差异性表达一致的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:经反转录实时定量聚合酶链式反应(RT-qPCR)技术验证,与基因芯片差异表达一致共有7个miRNAs,其中miR-30e-5p、miR-192-5p和miR-17-3p在皮损和血浆中表达均下调;miR-1227-5p、miR-125b-5p、miR-642a-5p和miR-29a-5p在皮损中表达上调,而血浆中表达下调。结论:差异表达的miRNA主要调控的靶基因及其基因功能与银屑病发病密切相关。     

p53基因沉默对HaCaT细胞MicroRNA表达谱的影响

目的 研究p53基因沉默前后HaCaT细胞microRNA（miRNA）的差异表达谱并进行相关功能分析。方法 利用慢病毒介导的RNAi对培养的HaCaT细胞株进行p53基因沉默,通过Trizol法抽提细胞总RNA,PEG（聚乙二醇）方法分离miRNA,T4RNA连接酶荧光标记后进行miRNA芯片杂交,利用Genepix 4000B 图像分析软件和Genepix Pro 6.0软件进行数据分析,生物信息学方法检索出p53基因沉默前后HaCaT细胞差异表达的miRNA调控的靶基因,选取每个miRNA调控的前20个靶基因进行靶基因功能及KEGG分析。结果 p53基因沉默前后HaCaT细胞中发现53个差异表达的miRNA,其中41个表达上调,12个下调（差异 ＞ 2倍）。上调超过200倍的miRNA有：hsa-miR-141-3p、hsa-miR-15a-5p、hsa-miR-27a-3p、hsa-miR-130b-3p、hsa-miR-19a-3p;下调超过75%的miRNA有：hiv1-miR-TAR-3p、hsa-miR-630、hsa-miR-1246、hsa-miR-1275。靶基因预测和靶基因KEGG分析结果显示,部分靶基因与MAPK信号通路、代谢通路、肿瘤侵袭等有关。结论 hsa-miR-141-3p等9个miRNA及其调控的靶基因可能参与p53的分子调控。 【关键词】 基因,p53; 角蛋白细胞; 微RNAs; 基因沉默; 芯片分析技术     

中波紫外线诱导小鼠皮肤光损伤中miRNA146a表达的研究

目的 探讨中波紫外线（UVB）诱导光损伤小鼠皮肤中miRNA146a表达的变化。方法 以C57/BL6小鼠为研究对象,分时间组和剂量组,剂量组分别以30、60、90、180、270 mJ/cm2 UVB照射小鼠背部皮肤,24 h后取材;时间组以180 mJ/cm2 UVB照射小鼠背部皮肤后,取1、12、24、48 h为检测时点。采用实时荧光定量PCR检测miRNA146a的表达水平,同时利用在线数据库targetscan等预测靶基因,并用Gostat软件对其进行功能分析。免疫组化技术检测可能与其功能相关的信号转导通路的关键蛋白STAT3,初步探讨其功能。结果 UVB照射后,空白组,30、60、90、180、270 mJ/cm2剂量组miRNA146a的表达水平分别为0.01158 ± 0.00098、0.01083 ± 0.00104、0.00872 ± 0.00031、0.00851 ± 0.00033、0.00810 ± 0.00057、0.00770 ± 0.00031,与UVB的辐射剂量呈负相关（r = -0.83,P ＜ 0.05）;而在时间组中,UVB照射1、12、24、48 h后miRNA146a的表达水平分别为0.00730 ± 0.00036、0.00805 ± 0.00035、0.00810 ± 0.00057、0.00837 ± 0.00039,与对照组相比均有下调（P ＜ 0.05）。Gostat分析显示,miRNA146a主要与细胞生长分化以及多种信号转导途径相关。免疫组化结果提示,在高剂量UVB辐射时,磷酸化STAT3表达更为强烈。结论 miRNA146a可能在UVB诱导的光损伤机制中具有关键作用,主要体现与炎症负调控有关,可能通过JAK-STAT3信号转导途径起作用。     

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.     

降钙素基因相关肽对朗格汉斯细胞功能影响的研究进展

在慢性炎症性皮肤病的神经免疫调节过程中,神经肽对于皮肤免疫细胞的调节作用受到越来越多的重视.在精神紧张、应激和压力的作用下,皮肤局部神经纤维产生降钙素基因相关肽,调节皮肤的朗格汉斯细胞.朗格汉斯细胞是表皮中重要的专职抗原提呈细胞.近年来发现,降钙素基因相关肽不仅可以影响朗格汉斯细胞的增殖、分化,而且影响其抗原提呈功能.降钙素基因相关肽可以抑制朗格汉斯细胞核因子κB通路的活化、抑制其协同刺激分子的表达,进而影响朗格汉斯细胞介导的免疫反应.     

miRNA miR‐17‐92 cluster is differentially regulated in the imiqumod‐treated skin but is not required for imiqumod‐induced psoriasis‐like dermatitis in mice

MicroRNAs (miRNAs) play very important roles in the control of immune cell and keratinocyte development and function and are implicated in skin inflammatory diseases, including psoriasis. miRNA miR‐17‐92 was reported to promote the differentiation of Th1 and Th1 cells and to regulate cell proliferation and apoptosis. Here we showed that imiquimod (IMQ) differentially regulates the expression of miR‐17‐92 cluster in the mouse skin, upregulating miR‐17 and miR‐19 families and downregulating miR‐92. To investigate whether miR‐17‐92 cluster is functionally involved in the psoriasis, we have generated three mutant mice with specific deletion or overexpression of miR‐17‐92 cluster in keratinocytes, or with deletion of miR‐17‐92 cluster in T cells. Interestingly, deletion or overexpression of miR‐17‐92 cluster in keratinocytes, or deletion of miR‐17‐92 in T cells did not significantly affect IMQ‐induced psoriasis‐like dermatitis development in the mutant mice compared with wild‐type littermates. Thus, miRNA miR‐17‐92 cluster may not be a key factor regulating imiqumod‐induced psoriasis‐like dermatitis.     

Differential expression analysis of miRNA in peripheral blood mononuclear cells of patients with non‐segmental vitiligo

Vitiligo is a common depigmentary skin disease that may follow a pattern of multifactorial inheritance. The essential factors of its immunopathogenesis is thought to be the selective destruction of melanocytes. As a new class of microregulators of gene expression, miRNA have been reported to play vital roles in autoimmune diseases, metabolic diseases and cancer. This study sought to characterize the different miRNA expression pattern in the peripheral blood mononuclear cells (PBMC) of patients with non‐segmental vitiligo (NSV) and healthy individuals and to examine their direct responses to thymosin α1 (Tα1) treatment. The miRNA expression profile in the PBMC of patients with NSV was analyzed using Exiqon's miRCURY LNA microRNA Array. The differentially expressed miRNA were validated by real‐time quantitative polymerase chain reaction. We found that the expression levels of miR‐224‐3p and miR‐4712‐3p were upregulated, and miR‐3940‐5p was downregulated in the PBMC. The common clinical immune modulator Tα1 changed the miRNA expression profile. Our analysis showed that differentially expressed miRNA were associated with the mechanism of immune imbalance of vitiligo and that Tα1 could play an important role in changing the expression of these miRNA in the PBMC of patients with NSV. This study provided further evidence that miRNA may serve as novel drug targets for vitiligo therapeutic evaluation.     

Reproducible pattern of microRNA in normal human skin

Please cite this paper as: Reproducible pattern of microRNA in normal human skin. Experimental Dermatology 2010; 19 : e201–e205. Abstract: MicroRNAs (miRNAs) regulate cell growth, differentiation and apoptosis via specific targeting of messenger RNA (mRNA). Aberrant mRNA expression contributes to pathological processes such as carcinogenesis. To take advantage of miRNA profiling in skin disease it is essential to investigate miRNA expression pattern in normal human skin. Here we investigated miRNA expression profiles from skin biopsies of 8 healthy volunteers taken from sun protected and mildly photo damaged skin using the modified protocol for miRNA extraction. We were able to show a constant pattern of miRNA expression between different individuals. We did not find any significant differences in miRNA expression between sun protected and mildly photodamaged skin. These results may be valuable for future design of studies on miRNA expression in skin disease.     

Serum miRNA expression profiles change in autoimmune vitiligo in mice

It is widely believed that non‐segmental vitiligo results from the autoimmune destruction of melanocytes. MicroRNAs (miRNAs), a class of small non‐coding RNAs that negatively regulate gene expression, are involved in the immune cell development and function and regulate the development of autoimmune diseases. Recent studies demonstrate that functional miRNAs can be detected in the serum and serve as biomarkers of various diseases. In the present study, we used a mouse autoimmune vitiligo model, in which melanocyte autoreactive CD4⁺ T cells were adoptively transferred into Rag1^?/? host mice. Serum miRNA expression was profiled in vitiligo developed mice and control mice using TaqMan RT‐PCR arrays. We have found that the expressions of 20 serum miRNAs were changed in vitiligo mice compared to control mice. Three increased miRNAs, miR‐146a, miR‐191, and miR‐342‐3p, were further confirmed by a single TaqMan RT‐PCR. Our findings suggest that miRNAs may be involved in vitiligo development and serum miRNAs could serve as serum biomarkers for vitiligo in mice.