Clinical trait-connected network analysis reveals transcriptional markers of active psoriasis treatment with Liangxue-Jiedu decoction
Clinical trait-connected network analysis reveals transcriptional markers of active psoriasis treatment with Liangxue-Jiedu decoction
复制标题
临床性状关联网络分析揭示凉血解毒汤治疗活动性银屑病的转录标志物
DOI：
10.1016/j.jep.2020.113551
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发表时间：
2021-01-15
影响因子：
5.4
通讯作者：
Li, Ping
中科院分区：
文献类型：
--
作者：
Li, Ya-Jun;Zhou, Tao;Li, Ping
民族药理学相关性：银屑病是一种复杂的复发性炎症性皮肤病，在不同阶段具有不同的病理变化。活动期的牛皮癣相当于中医的血热型，中医凉血解毒汤治疗牛皮癣数十年，疗效确切。根据中医理论，LJD具有清热凉血的功能。研究目的：我们旨在研究与活动期银屑病相关的分子特征，并鉴定对LJD治疗伴随皮损缓解有反应的基因。材料和方法：招募符合特定诊断标准的健康志愿者和银屑病患者。对 10 名银屑病患者（治疗前和治疗后）和 6 名健康志愿者的外周血单核细胞 (PBMC) 的 26 个转录组进行了分析。采用差异基因表达分析（DGEA）和加权基因共表达网络分析（WGCNA）相结合的综合方法对RNA测序数据进行分析，其中基因表达与多种临床特征相关，包括银屑病面积和严重程度指数（PASI）以及皮损改善率（Delta PASI）。然后使用体外细胞测定结合流式细胞术分析和 RT-PCR 验证 LJD 的作用。 结果：我们确定了四个具有统计显着性的网络模块 (P < 0.05)，其中两个与 PASI 评分相关，另外两个分别与 8 周治疗和 Delta PASI 相关。在银屑病患者中，与健康人相比，炎症通路的激活和G蛋白信号传导基因（GTPase IMAP家族成员和G蛋白偶联受体）的抑制同时存在，CD83和CD69高表达，CD160和CD180低表达。随着 LJD 治疗和病变缓解，CD69 和细胞周期相关基因（包括 CCNA2、CCNB2、CDK1 和 TOP2A）的表达下调。 LJD 对 CD69 表达的抑制作用通过激活幼稚 CD4(+) T 淋巴细胞的下降得到证实。结论：我们的研究表明，活动性银屑病的特点是免疫状态不平衡，树突细胞和淋巴细胞相关的炎症激活以及 NK 细胞和 B 细胞相关的防御反应异常。 LJD 在 T 细胞激活中发挥抑制作用，T 细胞激活是银屑病病理级联下游的一个过程。
Ethnopharmacological relevance: Psoriasis is a complex recurrent inflammatory skin disease with different pathological changes in different stages. Psoriasis in its active stage, which is comparable to the blood-heat type in traditional Chinese medicine (TCM), has been treated by Liangxue Jiedu Decoction (LJD) in TCM for decades, with proven efficacy. According to TCM theories, LJD has the function of removing heat and pathogenic factors from the blood.Aim of the study: We aimed to investigate the molecular features associated with the active stage psoriasis and identify genes responding to LJD treatment accompanied by lesion remission.Materials and methods: Healthy volunteers and psoriasis patients who met specific diagnostic criteria were recruited. Twenty-six transcriptomes were profiled from the peripheral blood mononuclear cells (PBMCs) of 10 psoriasis patients (preand post-treatment) and 6 healthy volunteers. RNA sequencing data were analyzed using an integrated approach combining differential gene expression analysis (DGEA) and weighted gene co-expression network analysis (WGCNA), by which gene expression was linked to multiple clinical traits, including psoriasis area and severity index (PASI), as well as the improvement rate of skin lesions (Delta PASI). The actions of LJD were then verified using an in vitro cell assay coupled to flow cytometric analysis and RT-PCR.Results: We identified four network modules with statistical significance (P < 0.05), two of which connected to the PASI score, while the other two connected to 8-week treatment and Delta PASI, respectively. In psoriasis patients, activated inflammatory pathways and inhibited G-protein signaling genes (GTPase IMAP family member and G protein-coupled receptor) co-occurred, with high expression of CD83 and CD69, and low expression of CD160 and CD180, compared with the health. Accompanying LJD treatment and lesion remission, the expression of CD69 and cell cycle-related genes, including CCNA2, CCNB2, CDK1, and TOP2A, was down-regulated. The inhibitory role of LJD on CD69 expression was confirmed by the decline of activating naive CD4(+) T lymphocytes.Conclusion: Our study suggests that active psoriasis is characterized by unbalanced immune status with dendrite cell and lymphocyte-associated inflammatory activation as well as NK celland B cell-associated defense response aberrance. LJD played an inhibitory role in T cell activation, a process located downstream pathological cascade of psoriasis.