LncRNA-MSX2P1通过ROS/MAPK/自噬信号通路在银屑病中的调控作用

Immune dysfunction is an important part in the pathogenesis of psoriasis. Inflammatory response mediated by T cells and immune molecules plays important role in promoting the occurrence and development of psoriasis.The long noncoding RNA (lncRNA) are a class of long non-coding RNA , lncRNA can regulate gene expression at various levels.MAPK (mitogen-activated protein kinase) signaling pathway plays an important role in inflammation. The generation of reactive oxygen species (ROS) can induce autophagy and signaling pathway inducing autophagy is usually related to MAPK.In our previous study, the results showed that IL-22 treatment can promote the expression of lncRNA-MSX2P1 in HaCaT and primary cultured keratinocyte. lncRNA-MSX2P1 knockdown can suppress the expression of inflammatory factors,such as IL-23, NF-κB, TNF-αand IL-12β,suppress cell proliferation and promote cell apoptosis. lncRNA-MSX2P1 knockdown can activate cell autophagy in HaCaT. Based on our previous study, we present below scientific hypotheses: lncRNA-MSX2P1 knockdown can suppress the expression of inflammatory factors through activating ROS/MAPK/autophagy signaling pathway to influence occurrence of psoriasis. In this study, we will investigate the function of lncRNA-MSX2P1-ROS/MAPK/autophagy signaling axis in occurrence of psoriasis by Lentivirus transfection, flow cytometry ,western blot and transmission electron microscopy experimental method.

免疫功能紊乱是银屑病发病机制中的重要环节,T细胞及免疫活性分子介导的炎症反应发挥重要作用.LncRNA是一类从多层面调控基因表达的长链非编码RNA分子;MAPK信号通路在炎症反应中发挥重要作用;活性氧（ROS）能激活自噬，激活自噬的信号通路和MAPK密切相关.我们前期研究发现IL-22处理的HaCaT细胞及原代角质形成细胞lncRNA-MSX2P1高表达;干扰lncRNA-MSX2P1表达抑制炎症因子IL-23, NF-κB, TNF-α, IL-12β的表达,抑制增殖,促进凋亡;干扰lncRNA-MSX2P1表达可激活HaCaT细胞自噬.因此我们提出如下科学假说:通过干扰lncRNA-MSX2P1可激活ROS/MAPK/自噬信号通路,抑制炎症因子表达,从而影响银屑病的发生.本研究将采用慢病毒转染、流式细胞仪、WB、透射电镜等实验方法探讨lncRNA-MSX2P1在银屑病发病中的调控作用.

背景：LncRNA在银屑病发病中发挥着重要的调控作用。.目的：探讨LncRNA-MSX2P1、SPRR2C、LncRNA H19 (H19)及lnc-FRA10AC1-3:1银屑病角质形成细胞中的作用机制。 .方法：FISH和qRT-PCR检测了LncRNA-MSX2P1, SPRR2C、LncRNA H19 (H19)及lnc-FRA10AC1-3:1的表达和亚细胞定位。CCK-8、CFSE、流式细胞术等方法检测LncRNA-MSX2P1, SPRR2C、LncRNA H19 (H19)及lnc-FRA10AC1-3:1在角质形成细胞增殖及银屑病炎症反应中的调控作用。.结果：LncRNA-MSX2P1基因的表达水平与氧化应激水平负相关。LncRNA-MSX2P1参与调控角质形成细胞MAPK信号转导通路。干扰lncRNA-MSX2P1 的表达能够促进Beclin1 和LC3B 的表达，促进自噬。 .SPRR2C在银屑病样本和m5诱导的银屑病角质形成细胞中高度表达。SPRR2C的亚细胞定位主要集中在细胞质中。SPRR2C调控角质形成细胞的增殖、细胞周期和凋亡。SPRR2C促进角质形成细胞中IL-1β、IL-6、IL-8、CXCL2和CCL20的表达。PI3K/AKT/mTOR信号通路参与了SPRR2C的作用。AKT特异抑制剂MK-2206可以抑制SPRR2C过表达的调控。.H19通过抑制miR-766-3p，间接激活S1PR3的表达和抑制IL-17A和IL-22的分泌，发挥抑制角质形成细胞增殖、炎症的作用，通过AKT/mTOR通路促进银屑病进程。.lnc-FRA10AC1-3:1在银屑病样本和m5诱导的银屑病角质形成细胞中高度表达。lnc-FRA10AC1-3:1调控角质形成细胞的增殖、细胞周期和凋亡。lnc-FRA10AC1-3:1促进角质形成细胞中CXCL9的表达。.结论：我们的研究结果表明，LncRNA-MSX2P1, SPRR2C、LncRNA H19 (H19)及lnc-FRA10AC1-3:1在银屑病角质形成细胞中发挥调控作用，参与自噬相关信号通路及PI3K/AKT/mTOR信号通路，可能为银屑病的诊断和治疗提供一个潜在的靶点。