Department of Rheumatology and Immunology, The First Hospital of Jilin University, Changchun, China.
Division of Clinical Research, The First Hospital of Jilin University, Changchun, China.
J Oral Pathol Med. 2022 Oct;51(9):818-828. doi: 10.1111/jop.13355. Epub 2022 Oct 9.
Primary Sjögren's syndrome is characterized by lymphocytic infiltration and dysfunction of exocrine glands. The persistent presence of lymphocytes in these glands is an important cause of injury to glandular epithelial cells. MicroRNAs play an important role in primary Sjögren's syndrome and regulate mRNA expression. This study evaluated the expression of microRNA related to lymphocyte infiltration in primary Sjögren's syndrome patients so as to find novel diagnostic and therapeutic targets for primary Sjögren's syndrome. We also explored the microRNA-mRNA networks related to lymphocyte infiltration.
mRNA-seq and microRNA-seq of peripheral blood mononuclear cells (PBMCs) were performed on samples from five primary Sjögren's syndrome patients and five matched healthy controls. Meanwhile, microRNA-mRNA network analysis was also conducted. RT-qPCR was used for validation of differentially expressed RNAs. Immunohistochemistry analysis was used to detect MMP2 expression in labial gland tissue. Hsa-miR-3202 mimics/inhibitor-transfected Jurkat cells were used to measure the effects of hsa-miR-3202 on the infiltration potential of T cells.
mRNA and microRNA sequencing revealed that 84 differentially expressed mRNAs and 49 differentially expressed microRNAs had a mutual regulatory relationship. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that differentially expressed MMP2 and its related microRNA, hsa-miR-3202, were enriched in the leukocyte transendothelial migration pathway. MMP2 was highly expressed in PBMC and labial gland tissue in primary Sjögren's syndrome patients. Hsa-miR-3202 was lower expressed in primary Sjögren's syndrome than healthy control. Furthermore, hsa-miR-3202 mimics transfection decreased MMP2 expression in Jurkat cells, and inhibited Jurkat cells invasion (p = 0.047).
Large number of differentially expressed microRNAs and mRNAs were detected in primary Sjögren's syndrome, and these differentially expressed microRNAs and mRNAs had a mutual regulatory relationship and played an important role in primary Sjögren's syndrome. In the study, we found hsa-miR-3202 regulate MMP2 and inhibited the infiltration of T cells from peripheral blood into the gland, which played a protective role.
原发性干燥综合征的特征是淋巴细胞浸润和外分泌腺功能障碍。这些腺体中持续存在的淋巴细胞是导致腺上皮细胞损伤的重要原因。MicroRNAs 在原发性干燥综合征中发挥着重要作用，并调节 mRNA 的表达。本研究评估了与原发性干燥综合征患者淋巴细胞浸润相关的 microRNA 的表达，以期为原发性干燥综合征找到新的诊断和治疗靶点。我们还探讨了与淋巴细胞浸润相关的 microRNA-mRNA 网络。
对 5 例原发性干燥综合征患者和 5 例匹配的健康对照者的外周血单个核细胞 (PBMC) 样本进行 mRNA-seq 和 microRNA-seq 检测，同时进行 microRNA-mRNA 网络分析。采用 RT-qPCR 验证差异表达 RNA。采用免疫组织化学分析检测唇腺组织中 MMP2 的表达。采用 Jurkat 细胞转染 hsa-miR-3202 模拟物/抑制剂，检测 hsa-miR-3202 对 T 细胞浸润潜力的影响。
mRNA 和 microRNA 测序显示，84 个差异表达的 mRNAs 和 49 个差异表达的 microRNAs 存在相互调节关系。京都基因与基因组百科全书 (KEGG) 分析表明，差异表达的 MMP2 及其相关 microRNA hsa-miR-3202 富集在白细胞跨内皮迁移途径中。MMP2 在原发性干燥综合征患者的 PBMC 和唇腺组织中高表达。原发性干燥综合征患者的 hsa-miR-3202 表达水平低于健康对照者。此外，hsa-miR-3202 模拟物转染降低了 Jurkat 细胞中的 MMP2 表达，并抑制了 Jurkat 细胞的侵袭（p=0.047）。
原发性干燥综合征患者中检测到大量差异表达的 microRNAs 和 mRNAs，这些差异表达的 microRNAs 和 mRNAs 存在相互调节关系，在原发性干燥综合征中发挥着重要作用。在本研究中，我们发现 hsa-miR-3202 调节 MMP2 并抑制外周血 T 细胞浸润腺体，发挥保护作用。
