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Journal of Peking University (Health Sciences) ›› 2023, Vol. 55 ›› Issue (6): 1022-1027. doi: 10.19723/j.issn.1671-167X.2023.06.010

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

Wen-gen LI1,*(),Xiao-dong GU2,Rui-qiang WENG2,Su-dong LIU2,Chao CHEN1   

  1. 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:2023-08-18 Online:2023-12-18 Published:2023-12-11
  • Contact: Wen-gen LI E-mail:ligen0072008@163.com
  • 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)

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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).

Key words: Systemic sclerosis, microRNAs, Exosomes, Interstitial lung disease

CLC Number: 

  • R593.25

Table 1

Demographic and clinical parameters of SSc patients and healthy controls"

Variables SSc (n=20) Healthy controls (n=15)
lcSSc (n=13) dcSSc (n=7)
Age/years 53.8±11.4 50.1±15.2 49.1±6.4
Male/Female, n 4/9 3/4 4/11
Raynaud phenomenon 10 (76.9) 4 (57.1) n/a
Arthritis 7 (53.8) 4 (57.1) n/a
Digital ulcers 2 (15.4) 0 (0) n/a
ILD 5 (38.5) 2 (28.6) n/a
ESR/(mm/h) 26.0 (15.0, 38.0) 24.0 (6.5, 48.5) n/a
CPR/(g/L) 1.5 (0.9, 7.3) 2.5 (1.2, 19.5) n/a
ANA positive 13 (100.0) 7 (100.0) n/a
Anti-Scl-70 antibody 8 (61.5) 3 (42.9) n/a
ACA 3 (23.1) 0 (0) n/a
Anti-Ro-52 antibody 2 (15.4) 3 (42.9) n/a
Rodman assessment 5.0±2.4 15.4±4.8** n/a

Table 2

Clinical characteristics of ILD and non-ILD subgroups among SSc patients"

Variables ILD (n=7) NILD (n=13)
Age/years 51.1±10.8 53.4±13.8
Male/Female, n 0/7 7/6
Raynaud phenomenon 6 (85.7) 8 (61.5)
Arthritis 4 (57.1) 7 (53.8)
Digital ulcers 1 (14.3) 1 (7.7)
ESR/(mm/h) 38.0 (21.0, 47.5) 18.0 (10.0, 38.0)
CPR/(g/L) 1.4 (0.9, 4.9) 1.8 (1.1, 18.3)
ANA 7 (100.0) 13 (100.0)
Anti-Scl-70 antibody 5 (71.4) 6 (46.2)
ACA 0 (0) 3 (23.1)
Anti-Ro-52 antibody 2 (28.6) 3 (23.1)
Rodman assessment 9.0±7.1 9.9±7.1

Figure 1

Identification of plasma derived exosomes A, analysis of exosomes by markers CD63 and TSG101 using Western blot; B, exosomes were observed under transmission electron microscope (arrows). EDS, exosome deprived supernatant."

Figure 2

Comparison of expression of plasma exosomal miRNAs between the groups A, comparison of expression of miR-34-5p, miR-92-3p and miR-142-3p between SSc patients and healthy controls; B, comparison of expression of exosomal miR-34-5p, miR-92-3p and miR-142-3p between lcSSc and dcSSc patients; C, comparison of expression of miR-34-5p, miR-92-3p and miR-142-3p between SSc patients with ILD and without ILD. SSc, systemic sclerosis; HCs, healthy controls; dcSSc, diffuse cutaneous systemic sclerosis; lcSSc, limited cutaneous systemic sclerosis; ILD, interstitial lung disease; NILD, non-ILD."

Table 3

Spearman's rank correlation coefficients between exosomal miRNAs and clinical parameters in SSc patients"

Variables miR-34-5p miR-92-3p miR-142-3p
r P r P r P
Raynaud phenomenon 0.19 0.424 0.00 >0.999 0.13 0.578
Arthritis -0.46 0.040* 0.13 0.583 -0.48 0.032*
ILD -0.48 0.031* 0.08 0.732 -0.55 0.011*
ESR -0.41 0.075 -0.18 0.438 -0.55 0.012*
CPR -0.11 0.640 -0.10 0.686 -0.05 0.821
Anti-Scl-70 antibody -0.35 0.126 -0.44 0.051 -0.18 0.455
ACA 0.13 0.575 0.09 0.722 0.26 0.278
Anti-Ro-52 antibody 0.15 0.523 0.30 0.193 0.13 0.585
Rodman assessment 0.23 0.336 0.20 0.406 0.20 0.394
1 Denton CP , Khanna D . Systemic sclerosis[J]. Lancet, 2017, 390 (10103): 1685- 1699.
doi: 10.1016/S0140-6736(17)30933-9
2 Szabo I , Muntean L , Crisan T , et al. Novel concepts in systemic sclerosis pathogenesis: Role for miRNAs[J]. Biomedicines, 2021, 9 (10): 1471.
doi: 10.3390/biomedicines9101471
3 Liu Y , Cheng L , Zhan H , et al. The roles of noncoding RNAs in systemic sclerosis[J]. Front Immunol, 2022, 13, 856036.
doi: 10.3389/fimmu.2022.856036
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.
doi: 10.1016/j.autrev.2019.102396
5 Zhao M , Qi Q , Liu S , et al. MicroRNA-34a: A novel therapeutic target in fibrosis[J]. Front Physiol, 2022, 13, 895242.
doi: 10.3389/fphys.2022.895242
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.
doi: 10.1093/rheumatology/kev234
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.
doi: 10.1080/08916934.2019.1621856
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.
doi: 10.1186/s12931-019-0980-7
10 Duan W , Zhang W , Jia J , et al. Exosomal microRNA in autoimmunity[J]. Cell Mol Immunol, 2019, 16 (12): 932- 934.
doi: 10.1038/s41423-019-0319-9
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.
doi: 10.1016/j.jneuroim.2021.577640
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.
doi: 10.1165/rcmb.2016-0163OC
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.
doi: 10.3390/ijms21062228
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.
doi: 10.1371/journal.pone.0158367
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.
doi: 10.1016/j.gene.2015.02.065
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.
doi: 10.3390/cells10112836
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.
doi: 10.3899/jrheum.140502
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.
doi: 10.1093/rheumatology/kes120
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.
doi: 10.1136/thoraxjnl-2019-214077
22 Njock MS , Guiot J , Henket MA , et al. Sputum exosomes: Promising biomarkers for idiopathic pulmonary fibrosis[J]. Thorax, 2019, 74 (3): 309- 312.
doi: 10.1136/thoraxjnl-2018-211897
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