论著

血浆外泌体miR-34-5p和miR-142-3p在系统性硬化症中的表达及临床意义

  • 李文根 ,
  • 古晓东 ,
  • 翁锐强 ,
  • 刘苏东 ,
  • 陈超
展开
  • 1. 梅州市人民医院(黄塘医院)风湿免疫科,广东梅州 514031
    2. 梅州市人民医院(黄塘医院)科研实验中心,广东梅州 514031

收稿日期: 2023-08-18

  网络出版日期: 2023-12-11

基金资助

广东省医学科学技术研究基金(B2022263);梅州市人民医院科研人才培育项目(PY-C2020009)

Expression and clinical significance of plasma exosomal miR-34-5p and miR-142-3p in systemic sclerosis

  • Wen-gen LI ,
  • Xiao-dong GU ,
  • Rui-qiang WENG ,
  • Su-dong LIU ,
  • Chao CHEN
Expand
  • 1. Department of Rheumatology and Immunology, Meizhou People's Hospital (Huangtang Hospital), Meizhou 514031, Guangdong, China
    2. Scientific Research and Experimental Center, Meizhou People's Hospital (Huangtang Hospital), Meizhou 514031, Guangdong, China

Received date: 2023-08-18

  Online published: 2023-12-11

Supported by

the Medical Science and Technology Research Foundation of Guangdong Province(B2022263);the Scientific Research Talent Cultivation Foundation of Meizhou People's Hospital(PY-C2020009)

摘要

目的: 检测系统性硬化症(systemic sclerosis,SSc)患者血浆外泌体微小RNA(microRNA,miRNA)的表达,探讨其在SSc中的临床意义。方法: 选取20例梅州市人民医院风湿免疫科2020年1月至2022年1月未接受治疗的初诊SSc患者,同时以年龄及性别匹配的15例健康志愿者作为对照组。采用超速离心法获得血浆外泌体,采用实时荧光定量聚合酶链式反应(quantative real-time polymerase chain reaction, qRT-PCR)检测外泌体miR-34-5p、miR-92-3p和miR-142-3p的表达。采用Spearman秩相关系数检验分析miRNA表达水平与SSc临床特点的相关性。结果: 20例SSc患者的平均年龄为(52.6±12.6)岁,男性7例,女性13例。根据皮肤累及范围,13例为局限皮肤型SSc (limited cutaneous systemic sclerosis, lcSSc),7例为弥漫皮肤型SSc (diffuse cutaneous systemic sclerosis, dcSSc)。根据高分辨率胸部CT检查结果,7例确诊间质性肺病(interstitial lung disease, ILD),13例确诊非ILD。SSc患者血浆外泌体miR-34-5p、miR-92-3p和miR-142-3p的表达水平显著高于对照组(分别为P=0.003、P=0.000 1和P=0.016)。与未并发ILD的患者相比,并发ILD患者miR-34-5p和miR-142-3p的表达水平显著降低(分别为P=0.037和P=0.015)。miR-34-5p和miR-142-3p的表达水平与ILD(分别为r=-0.48、P=0.031和r=-0.55、P=0.011)、关节炎(分别为r=-0.46、P=0.040和r=-0.48、P=0.032)均呈负相关。miR-142-3p与红细胞沉降率呈负相关(r=-0.55、P=0.012)。结论: SSc的血浆外泌体miR-34-5p、miR-92-3p和miR-142-3p存在表达失调,表达异常的miR-34-5p和miR-142-3p与SSc相关ILD(SSc associated ILD, SSc-ILD)存在相关性。

本文引用格式

李文根 , 古晓东 , 翁锐强 , 刘苏东 , 陈超 . 血浆外泌体miR-34-5p和miR-142-3p在系统性硬化症中的表达及临床意义[J]. 北京大学学报(医学版), 2023 , 55(6) : 1022 -1027 . DOI: 10.19723/j.issn.1671-167X.2023.06.010

Abstract

Objective: To detect the expression of plasma exosomal microRNA (miRNA) in systemic sclerosis (SSc), and to investigate its clinical significance. Methods: A total of 20 patients who were initially diagnosed with SSc and did not receive medication in Department of Rheumatology and Immunology of Meizhou People' s Hospital from January 2020 to January 2022 were recruited, as well as 15 healthy individuals whose gender and age matched with those of the SSc patients. Plasma exosomes were isolated using ultracentrifugation method. The expression levels of exosomal miR-34-5p, miR-92-3p and miR-142-3p were detected by quantative real-time polymerase chain reaction (qRT-PCR). Correlations between the expression levels of exosomal miRNAs and clinical characteristic were analyzed by Spearman's rank correlation coefficient test. Results: The mean age of 20 patients with SSc was (52.6±12.6) years, including 7 males and 13 females. Among the 20 SSc patients, 13 cases were diagnosed as limited cutaneous systemic sclerosis (lcSSc) and 7 cases were diagnosed as diffuse cutaneous systemic sclerosis (dcSSc) according to the extent of skin involvement. According to the findings of high resolution chest CT, 7 of 20 SSc patients were diagnosed with interstitial lung disease (ILD) and 13 SSc patients were diagnosed with non-ILD. The expression levels of exosomal miR-34-5p, miR-92-3p and miR-142-3p were significantly elevated in the SSc patients compared with those in the healthy controls group (P=0.003, P=0.000 1, and P=0.016, respectively). Compared with the SSc patients without ILD, the expression levels of miR-34-5p and miR-142-3p were significantly lower in the SSc patients with ILD (P=0.037 and P=0.015, respectively). The expression levels of exosomal miR-34-5p and miR-142-3p showed negative correlation with ILD (r=-0.48, P=0.031 and r=-0.55, P=0.011, respectively), and arthritis (r=-0.46, P=0.040 and r=-0.48, P=0.032, respectively). The expression levels of exosomal miR-142-3p showed a negative correlation with erythrocyte sedimentation rate (ESR) (r=-0.55, P=0.012). Conclusion: Plasma exosomal miR-34-5p, miR-92-3p and miR-142-3p were dysregulated in SSc. The dyregulation of exosomal miR-34-5p and miR-142-3p showed correlation with SSc associated ILD (SSc-ILD).

参考文献

1 Denton CP , Khanna D . Systemic sclerosis[J]. Lancet, 2017, 390 (10103): 1685- 1699.
2 Szabo I , Muntean L , Crisan T , et al. Novel concepts in systemic sclerosis pathogenesis: Role for miRNAs[J]. Biomedicines, 2021, 9 (10): 1471.
3 Liu Y , Cheng L , Zhan H , et al. The roles of noncoding RNAs in systemic sclerosis[J]. Front Immunol, 2022, 13, 856036.
4 Henry TW , Mendoza FA , Jimenez SA . Role of microRNA in the pathogenesis of systemic sclerosis tissue fibrosis and vasculopathy[J]. Autoimmun Rev, 2019, 18 (11): 102396.
5 Zhao M , Qi Q , Liu S , et al. MicroRNA-34a: A novel therapeutic target in fibrosis[J]. Front Physiol, 2022, 13, 895242.
6 Wuttge DM , Carlsen AL , Teku G , et al. Specific autoantibody profiles and disease subgroups correlate with circulating micro-RNA in systemic sclerosis[J]. Rheumatology (Oxford), 2015, 54 (11): 2100- 2107.
7 Jafarinejad-Farsangi S , Gharibdoost F , Farazmand A , et al. MicroRNA-21 and microRNA-29a modulate the expression of collagen in dermal fibroblasts of patients with systemic sclerosis[J]. Autoimmunity, 2019, 52 (3): 108- 116.
8 Shi J , Li F , Luo M , et al. Distinct roles of Wnt/β-catenin signaling in the pathogenesis of chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis[J]. Mediators Inflamm, 2017, 2017, 3520581.
9 Cottin V , Brown KK . Interstitial lung disease associated with systemic sclerosis (SSc-ILD)[J]. Respir Res, 2019, 20 (1): 13.
10 Duan W , Zhang W , Jia J , et al. Exosomal microRNA in autoimmunity[J]. Cell Mol Immunol, 2019, 16 (12): 932- 934.
11 Mirzaei R , Zamani F , Hajibaba M , et al. The pathogenic, therapeutic and diagnostic role of exosomal microRNA in the autoimmune diseases[J]. J Neuroimmunol, 2021, 358, 577640.
12 Wermuth PJ , Piera-Velazquez S , Jimenez SA . Exosomes isolated from serum of systemic sclerosis patients display alterations in their content of profibrotic and antifibrotic microRNA and induce a profibrotic phenotype in cultured normal dermal fibroblasts[J]. Clin Exp Rheumatol, 2017, 35 (Suppl 106): 21- 30.
13 Cui H , Ge J , Xie N , et al. miR-34a inhibits lung fibrosis by inducing lung fibroblast senescence[J]. Am J Respir Cell Mol Biol, 2017, 56 (2): 168- 178.
14 Bulvik R , Biton M , Berkman N , et al. Forefront: MiR-34a-knockout mice with wild type hematopoietic cells, retain persistent fibrosis following lung injury[J]. Int J Mol Sci, 2020, 21 (6): 2228.
15 Disayabutr S , Kim EK , Cha SI , et al. miR-34 miRNAs regulate cellular senescence in type Ⅱ alveolar epithelial cells of patients with idiopathic pulmonary fibrosis[J]. PLoS One, 2016, 11 (6): e0158367.
16 Yang G , Yang L , Wang W , et al. Discovery and validation of extracellular/circulating microRNAs during idiopathic pulmonary fibrosis disease progression[J]. Gene, 2015, 562 (1): 138- 144.
17 Blumer S , Fang L , Chen WC , et al. IPF-Fibroblast Erk1/2 acti-vity is independent from microRNA cluster 17-92 but can be inhibited by treprostinil through DUSP1[J]. Cells, 2021, 10 (11): 2836.
18 Steen SO , Iversen LV , Carlsen AL , et al. The circulating cell-free microRNA profile in systemic sclerosis is distinct from both healthy controls and systemic lupus erythematosus[J]. J Rheumatol, 2015, 42 (2): 214- 221.
19 黄赛赛, 王丹丹, 张卓亚, 等. 系统性硬化症患者血浆7种miRNA水平与脏器累及和临床指标的相关性[J]. 临床检验杂志, 2021, 39 (5): 358- 361.
20 Sing T , Jinnin M , Yamane K , et al. microRNA-92a expression in the sera and dermal fibroblasts increases in patients with scleroderma[J]. Rheumatology (Oxford), 2012, 51 (9): 1550- 1556.
21 Guiot J , Cambier M , Boeckx A , et al. Macrophage-derived exosomes attenuate fibrosis in airway epithelial cells through delivery of antifibrotic miR-142-3p[J]. Thorax, 2020, 75 (10): 870- 881.
22 Njock MS , Guiot J , Henket MA , et al. Sputum exosomes: Promising biomarkers for idiopathic pulmonary fibrosis[J]. Thorax, 2019, 74 (3): 309- 312.
文章导航

/