Naghavian Reza, Ghaedi Kamran, Kiani-Esfahani Abbas, Ganjalikhani-Hakemi Mazdak, Etemadifar Masoud, Nasr-Esfahani Mohammad Hossein
Division of Cellular and Molecular Biology, Department of Biology, Faculty of Sciences, University of Isfahan, Isfahan, Iran; Department of Cellular Biotechnology at Cell Science research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran.
Division of Cellular and Molecular Biology, Department of Biology, Faculty of Sciences, University of Isfahan, Isfahan, Iran; Department of Cellular Biotechnology at Cell Science research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran; Cellular and Molecular Immunology Research Center, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
PLoS One. 2015 May 4;10(5):e0124555. doi: 10.1371/journal.pone.0124555. eCollection 2015.
One of the main issues in pathogenesis of MS is Th17/Treg imbalance. There are growing interests in nominating miRNAs involved in Th17 cell differentiation, suggesting them as new therapeutic agents that may reduce progression of different autoimmune diseases specially MS.
We assessed transcript levels of miR-141 and miR-200a in MS patients, during relapsing and remitting phases. We also investigated possible role of miR-141, miR-200a in inducing differentiation to Th17 cells.
Forty RR-MS patient samples including relapsing (n=20) and remitting (n=20) phases were chosen. Expression level of miR-141 and miR-200a were measured by RT-q PCR and compared to healthy control group (n=10). In-silico analyses on miR-141 and miR-200a targetome showed involvement of both miRNAs in T helper cell differentiation pathways including TGF-β, mTOR and JAK/STAT.
We observed that percentage of RORγt+ CD4+ T cells increase in relapsing phase while FOXP3+ CD4+ increase in remitting phase of MS patients. Furthermore, both miR-141 and miR-200a show up-regulation in relapsing phase of MS patients compared to remitting and control groups. Interestingly, expression level of target genes of miR-141 and miR-200a, which were assessed through in-silico methods, show down-regulation in relapsing phase of MS patients.
According to our results, miR-141 and miR-200a may be key miRNAs in progression of symptoms of MS through inducing differentiation of Th17 cells and inhibiting differentiation to Treg cells. Our data suggest that these miRNAs may probably inhibit negative regulators of Th17 cell differentiation, thus promoting its differentiation.
多发性硬化症发病机制中的主要问题之一是Th17/Treg失衡。人们对确定参与Th17细胞分化的微小RNA（miRNA）越来越感兴趣，这表明它们可能是新型治疗药物，有望减缓包括多发性硬化症在内的各种自身免疫性疾病的进展。
我们评估了复发缓解型多发性硬化症（RR-MS）患者在复发期和缓解期的miR-141和miR-200a转录水平。我们还研究了miR-141、miR-200a在诱导Th17细胞分化中的可能作用。
选取40例RR-MS患者样本，包括复发期（n=20）和缓解期（n=20）。通过逆转录定量聚合酶链反应（RT-q PCR）检测miR-141和miR-200a的表达水平，并与健康对照组（n=10）进行比较。对miR-141和miR-200a靶标组进行的电子分析表明，这两种miRNA均参与了包括转化生长因子-β（TGF-β）、哺乳动物雷帕霉素靶蛋白（mTOR）和Janus激酶/信号转导及转录激活因子（JAK/STAT）在内的辅助性T细胞分化途径。
我们观察到，RR-MS患者复发期RORγt+ CD4+ T细胞百分比增加，而缓解期FOXP3+ CD4+ T细胞增加。此外，与缓解期和对照组相比，RR-MS患者复发期的miR-141和miR-200a均上调。有趣的是，通过电子方法评估的miR-141和miR-200a靶基因的表达水平在RR-MS患者复发期下调。
根据我们的结果，miR-141和miR-200a可能是通过诱导Th17细胞分化和抑制Treg细胞分化来推动MS症状进展的关键miRNA。我们的数据表明，这些miRNA可能会抑制Th17细胞分化的负调节因子，从而促进其分化。
