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Immunomodulatory mechanism of umbilical cord mesenchymal stem cells modified by miR-125b-5p in systemic lupus erythematosus
Received date: 2021-07-26
Online published: 2024-10-16
Supported by
Supported by the National Natural Science Foundation of China(81860294);Supported by the National Natural Science Foundation of China(81860295);the Natural Science Foundation of Inner Mongolia(2019MS08055);the Inner Mongolia Autonomous Region Science and Technology Plan Projects(201802089);the Inner Mongolia Autonomous Region Science and Technology Plan Projects(2019GG052)
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Objective: To investigate the mechanism of immunomodulatory effects of umbilical cord mesenchymal stem cells (UC-MSCs) modified by miR-125b-5p on systemic lupus erythematosus (SLE). Methods: The expression level of miR-125b-5p was detected by real-time fluorescence quantitative PCR in UC-MSCs and peripheral blood mononuclear cells (PBMCs) from SLE patients and health checkers. Annexin V-FITC/PI apoptosis detection kit was used to detect the effect of miR-125b-5p on apoptosis of UC-MSCs. MRL/lpr mice in each group were injected with UC-MSCs via tail vein, and T-lymphocyte subsets in the spleen of the MRL/lpr mice were detected by flow cytometry after 5 weeks. The expression levels of interleukin (IL)-4 and IL-17A in serum of MRL/lpr mice were detected by ELISA. Hematoxylin-eosin staining was used to observe the pathological manifestations of the lungs and kidneys of the MRL/lpr mice. Results: miR-125b-5p was significantly down-regulated in PBMCs of SLE patients compared with healthy controls (P < 0.01). Compared with the UC-MSCs group, the expression of miR- 125b-5p in UC-MSCs modified by miR-125b-5p group was increased (P < 0.01). The survival rate of UC-MSCs was significantly increased by miR-125b-5p (P < 0.01). Compared with the untreated group of MRL/lpr mice, the expression level of IL-4 in serum was increased (P < 0.05); the expression level of IL-17A was decreased (P < 0.05); the proportion of Th17 cells in the spleen of MRL/lpr mice was decreased (P < 0.05); the inflammatory cells infiltration and micro-thrombosis of lungs and kidneys of MRL/lpr mice were significantly reduced in the UC-MSCs modified by miR-125b-5p treatment group. Conclusion: UC-MSCs modified by miR-125b-5p have immunomodulatory effects on systemic lupus erythematosus.
Zhihui WU , Mingzhi HU , Qiaoying ZHAO , Fengfeng LV , Jingying ZHANG , Wei ZHANG , Yongfu WANG , Xiaolin SUN , Hui WANG . Immunomodulatory mechanism of umbilical cord mesenchymal stem cells modified by miR-125b-5p in systemic lupus erythematosus[J]. Journal of Peking University(Health Sciences), 2024 , 56(5) : 860 -867 . DOI: 10.19723/j.issn.1671-167X.2024.05.017
| 1 | Tsokos GC . Systemic lupus erythematosus[J]. N Engl J Med, 2011, 365 (22): 2110- 2121. |
| 2 | Relle M , Foehr B , Schwarting A . Epigenetic aspects of systemic lupus erythematosus[J]. Rheumatol Ther, 2015, 2 (1): 33- 46. |
| 3 | Basta F , Fasola F , Triantafyllias K , et al. Systemic lupus erythematosus (SLE) therapy: The old and the new[J]. Rheumatol Ther, 2020, 7 (3): 433- 446. |
| 4 | Sharabi A , Tsokos GC . T cell metabolism: New insights in systemic lupus erythematosus pathogenesis and therapy[J]. Nat Rev Rheumatol, 2020, 16 (2): 100- 112. |
| 5 | Muhammad Yusoff F , Wong KK , Mohd Redzwan N . Th1, Th2, and Th17 cytokines in systemic lupus erythematosus[J]. Autoimmunity, 2020, 53 (1): 8- 20. |
| 6 | Serakinci N , Fahrioglu U , Christensen R . Mesenchymal stem cells, cancer challenges and new directions[J]. Eur J Cancer, 2014, 50 (8): 1522- 1530. |
| 7 | Drela K , Lech W , Figiel-Dabrowska A , et al. Enhanced neuro-therapeutic potential of Wharton' s jelly-derived mesenchymal stem cells in comparison with bone marrow mesenchymal stem cells culture[J]. Cytotherapy, 2016, 18 (4): 497- 509. |
| 8 | Liu L , Wong CW , Han M , et al. Meta-analysis of preclinical studies of mesenchymal stromal cells to treat rheumatoid arthritis[J]. EBioMedicine, 2019, 47, 563- 577. |
| 9 | Qi J , Tang X , Li W , et al. Mesenchymal stem cells inhibited the differentiation of MDSCs via COX2/PGE2 in experimental sialadenitis[J]. Stem Cell Res Ther, 2020, 11 (1): 325. |
| 10 | Liu C , Zhang H , Tang X , et al. Mesenchymal stem cells promote the osteogenesis in collagen-induced arthritic mice through the inhibition of TNF-α[J]. Stem Cells Int, 2018, 2018, 4069032. |
| 11 | Choudhery MS , Badowski M , Muise A , et al. Donor age negatively impacts adipose tissue-derived mesenchymal stem cell expansion and differentiation[J]. J Transl Med, 2014, 12, 8. |
| 12 | Escacena N , Quesada-Hernández E , Capilla-Gonzalez V , et al. Bottlenecks in the efficient use of advanced therapy medicinal products based on mesenchymal stromal cells[J]. Stem Cells Int, 2015, 2015, 895714. |
| 13 | Fischer UM , Harting MT , Jimenez F , et al. Pulmonary passage is a major obstacle for intravenous stem cell delivery: The pulmonary first-pass effect[J]. Stem Cells Dev, 2009, 18 (5): 683- 692. |
| 14 | Abdelmohsen K , Gorospe M . Noncoding RNA control of cellular senescence[J]. Wiley Interdiscip Rev RNA, 2015, 6 (6): 615- 629. |
| 15 | Su T , Xiao Y , Xiao Y , et al. Bone marrow mesenchymal stem cells-derived exosomal MiR-29b-3p regulates aging-associated insulin resistance[J]. ACS Nano, 2019, 13 (2): 2450- 2462. |
| 16 | Meng Y , Eirin A , Zhu XY , et al. Micro-RNAs regulate metabolic syndrome-induced senescence in porcine adipose tissue-derived mesenchymal stem cells through the P16/MAPK pathway[J]. Cell Transplant, 2018, 27 (10): 1495- 1503. |
| 17 | Vishnoi A , Rani S . MiRNA biogenesis and regulation of diseases: An overview[J]. Methods Mol Biol, 2017, 1509, 1- 10. |
| 18 | Gong B , Zheng L , Lu Z , et al. Mesenchymal stem cells negatively regulate CD4+ T cell activation in patients with primary Sj?gren syndrome through the miRNA-125b and miRNA-155 TCR pathway[J]. Mol Med Rep, 2021, 23 (1): 43. |
| 19 | Xiu L , Xing Q , Mao J , et al. miRNA-125b-5p suppresses hypo-thyroidism development by targeting signal transducer and activator of transcription 3[J]. Med Sci Monit, 2018, 24, 5041- 5049. |
| 20 | 胡明智, 张晶莹, 杨国安, 等. miR-1-5p修饰脐带间充质干细胞对系统性红斑狼疮T淋巴细胞亚群的免疫调节[J]. 中国组织工程研究, 2021, 25 (31): 4928- 4938. |
| 21 | Gentile P , Sterodimas A . Adipose-derived stromal stem cells (ASCs) as a new regenerative immediate therapy combating coronavirus (COVID-19)-induced pneumonia[J]. Expert Opin Biol Ther, 2020, 20 (7): 711- 716. |
| 22 | Toyserkani NM , J?rgensen MG , Tabatabaeifar S , et al. Concise review: A safety assessment of adipose-derived cell therapy in cli-nical trials: A systematic review of reported adverse events[J]. Stem Cells Transl Med, 2017, 6 (9): 1786- 1794. |
| 23 | Chen C , Liang J , Yao G , et al. Mesenchymal stem cells upregulate Treg cells via sHLA-G in SLE patients[J]. Int Immuno-pharmacol, 2017, 44, 234- 241. |
| 24 | 张立民. 系统性红斑狼疮microRNA表达谱和功能的初步研究[D]. 北京: 中国协和医科大学, 2010. |
| 25 | Wang D , Huang S , Yuan X , et al. The regulation of the Treg/Th17 balance by mesenchymal stem cells in human systemic lupus erythematosus[J]. Mol Immunol, 2017, 14 (5): 423- 431. |
| 26 | Golpanian S , DiFede DL , Pujol MV , et al. Rationale and design of the allogeneiC human mesenchymal stem cells (hMSC) in patients with aging fRAilTy via intravenoUS delivery (CRATUS) study: A phase Ⅰ/Ⅱ, randomized, blinded and placebo controlled trial to evaluate the safety and potential efficacy of allogeneic human mesenchymal stem cell infusion in patients with aging frailty[J]. Oncotarget, 2016, 7 (11): 11899- 11912. |
| 27 | Yang J , Yang X , Zou H , et al. Oxidative stress and Treg and Th17 dysfunction in systemic lupus erythematosus[J]. Oxid Med Cell Longev, 2016, 2016, 2526174. |
| 28 | Li D , Guo B , Wu H , et al. Interleukin-17 in systemic lupus erythematosus: A comprehensive review[J]. Autoimmunity, 2015, 48 (6): 353- 361. |
| 29 | Chen DY , Chen YM , Wen MC , et al. The potential role of Th17 cells and Th17-related cytokines in the pathogenesis of lupus nephritis[J]. Lupus, 2012, 21 (13): 1385- 1396. |
| 30 | La Cava A . Tregs in SLE: An Update[J]. Curr Rheumatol Rep, 2018, 20 (2): 6. |
| 31 | Beringer A , Noack M , Miossec P . IL-17 in chronic inflammation: From discovery to targeting[J]. Trends Mol Med, 2016, 22 (3): 230- 241. |
| 32 | Dolff S , Bijl M , Huitema MG , et al. Disturbed Th1, Th2, Th17 and T(reg) balance in patients with systemic lupus erythematosus[J]. Clin Immunol, 2011, 141 (2): 197- 204. |
| 33 | Moseley TA , Haudenschild DR , Rose L , et al. Interleukin-17 family and IL-17 receptors[J]. Cytokine Growth Factor Rev, 2003, 14 (2): 155- 174. |
| 34 | Qu N , Xu M , Mizoguchi I , et al. Pivotal roles of T-helper 17-related cytokines, IL-17, IL-22, and IL-23, in inflammatory diseases[J]. Clin Dev Immunol, 2013, 2013, 968549. |
| 35 | Ghali JR , Holdsworth SR , Kitching AR . Targeting IL-17 and IL-23 in immune mediated renal disease[J]. Curr Med Chem, 2015, 22 (38): 4341- 4365. |
| 36 | Talaat RM , Mohamed SF , Bassyouni IH , et al. Th1/Th2/Th17/Treg cytokine imbalance in systemic lupus erythematosus (SLE) patients: Correlation with disease activity[J]. Cytokine, 2015, 72 (2): 146- 153. |
| 37 | Zickert A , Amoudruz P , Sundstr?m Y , et al. IL-17 and IL-23 in lupus nephritis: Association to histopathology and response to treatment[J]. BMC immunol, 2015, 16 (1): 7. |
| 38 | Jha AN , Singh VK , Kumari N , et al. IL-4 haplotype -590T, -34T and intron-3 VNTR R2 is associated with reduced malaria risk among ancestral indian tribal populations[J]. PLoS One, 2012, 7 (10): e48136. |
| 39 | Patterson D , Jones C , Hart I , et al. The human interleukin-1 receptor antagonist (IL1RN) gene is located in the chromosome 2q14 region[J]. Genomics, 1993, 15 (1): 173- 176. |
| 40 | Rapoport M , Bloch O . Systemic lupus erythematosus[J]. N Engl J Med, 2012, 366 (6): 574. |
| 41 | Tsokos GC , Lo MS , Costa Reis P , et al. New insights into the immunopathogenesis of systemic lupus erythematosus[J]. Nat Rev Rheumatol, 2016, 12 (12): 716- 730. |
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