Skip to main content

Advertisement

Log in

Different MicroRNA profiles in Peripheral Blood mononuclear cells from patients with initial-onset and recurrent vogt–Koyanagi–Harada Disease

  • Original Article
  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Background

Vogt–Koyanagi–Harada (VKH) disease is a common type of uveitis that leads to blindness. The clinical manifestations and treatment solutions are different between initial-onset and recurrent VKH. Therefore, identifying the microRNA (miRNA) profiles from initial-onset and recurrent VKH patients may shed light on the molecular mechanisms underlying the pathogenesis of VKH disease.

Methods and Results

RNAs isolated from peripheral blood mononuclear cells (PBMCs) from patients with initial-onset VKH, recurrent VKH, and healthy individuals were subjected to high-throughput miRNA sequencing. Pairwise analysis of miRNA sequencing data between groups was conducted to identify differentially expressed miRNAs (DEMs), which were verified using real-time quantitative polymerase chain reaction. After receiver operating characteristic analyses, we found that hsa-miR-4664-3p, hsa-miR-7704, hsa-miR-4504, and hsa-miR-206 may serve as biomarkers of different VKH stages. DEMs were classified into three groups based on their differential expression: DEMs in initial-onset stage, DEMs in recurrent stage, and DEMs common between both VKH stages (shared DEMs). Pathway enrichment analysis using the Kyoto Encyclopedia of Genes and Genomes identified the mitogen-activated protein kinase, tumor necrosis factor, and mechanistic target of rapamycin kinase pathways as significantly enriched among the target genes of recurrent stage and shared DEMs. Furthermore, we mapped a network of competing endogenous RNAs for hsa-miR-206, which we used to identify putative targets for VKH treatment.

Conclusion

Hsa-miR-4664-3p, hsa-miR-7704, hsa-miR-4504, and hsa-miR-206 may serve as biomarkers for different stages of VKH. Additionally, our competing endogenous RNA network of hsa-miR-206 provides a new direction for VKH treatment.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Moorthy RS, Inomata H, Rao NA (1995) Vogt-Koyanagi-Harada syndrome. Surv Ophthalmol 39(4):265–292. doi: https://doi.org/10.1016/s0039-6257(05)80105-5

    Article  CAS  PubMed  Google Scholar 

  2. Du L, Kijlstra A, Yang P (2016) Vogt-Koyanagi-Harada disease: Novel insights into pathophysiology, diagnosis and treatment. Prog Retin Eye Res 52:84–111. doi: https://doi.org/10.1016/j.preteyeres.2016.02.002

    Article  CAS  PubMed  Google Scholar 

  3. Yang P, Ren Y, Li B, Fang W, Meng Q, Kijlstra A (2007) Clinical characteristics of Vogt-Koyanagi-Harada syndrome in Chinese patients. Ophthalmology 114(3):606–614. doi: https://doi.org/10.1016/j.ophtha.2006.07.040

    Article  PubMed  Google Scholar 

  4. Nazari H, Rao NA (2012) Resolution of subretinal fluid with systemic corticosteroid treatment in acute Vogt-Koyanagi-Harada disease. Br J Ophthalmol 96(11):1410–1414. doi: https://doi.org/10.1136/bjophthalmol-2012-301857

    Article  PubMed  Google Scholar 

  5. Yamanaka E, Ohguro N, Yamamoto S, Nakagawa Y, Imoto Y, Tano Y (2002) Evaluation of pulse corticosteroid therapy for vogt-koyanagi-harada disease assessed by optical coherence tomography. Am J Ophthalmol 134(3):454–456. doi: https://doi.org/10.1016/s0002-9394(02)01575-1

    Article  CAS  PubMed  Google Scholar 

  6. O’Keefe GA, Rao NA (2017) Vogt-Koyanagi-Harada disease. Surv Ophthalmol 62(1):1–25. doi: https://doi.org/10.1016/j.survophthal.2016.05.002

    Article  PubMed  Google Scholar 

  7. Silpa-Archa S, Silpa-Archa N, Preble JM, Foster CS (2016) Vogt-Koyanagi-Harada syndrome: Perspectives for immunogenetics, multimodal imaging, and therapeutic options. Autoimmun rev 15(8):809–819. doi: https://doi.org/10.1016/j.autrev.2016.04.001

    Article  CAS  PubMed  Google Scholar 

  8. Abu El-Asrar AM, Al Mudhaiyan T, Al Najashi AA, Hemachandran S, Hariz R, Mousa A et al (2017) Chronic Recurrent Vogt-Koyanagi-Harada Disease and Development of ‘Sunset Glow Fundus’ Predict Worse Retinal Sensitivity. Ocul Immunol Inflamm 25(4):475–485. doi: https://doi.org/10.3109/09273948.2016.1139730

    Article  CAS  PubMed  Google Scholar 

  9. Abu El-Asrar AM, Al Tamimi M, Hemachandran S, Al-Mezaine HS, Al-Muammar A, Kangave D (2013) Prognostic factors for clinical outcomes in patients with Vogt-Koyanagi-Harada disease treated with high-dose corticosteroids. Acta Ophthalmol 91(6):e486–e493. doi: https://doi.org/10.1111/aos.12127

    Article  CAS  PubMed  Google Scholar 

  10. Chang R, Yi S, Tan X, Huang Y, Wang Q, Su G et al (2018) MicroRNA-20a-5p suppresses IL-17 production by targeting OSM and CCL1 in patients with Vogt-Koyanagi-Harada disease. Br J Ophthalmol 102(2):282–290. doi: https://doi.org/10.1136/bjophthalmol-2017-311079

    Article  PubMed  Google Scholar 

  11. Shu J, Su G, Zhang J, Liu Z, Chang R, Wang Q et al (2021) Analyses of circRNA and mRNA Profiles in Vogt-Koyanagi-Harada Disease. Front Immunol 12:738760. doi: https://doi.org/10.3389/fimmu.2021.738760

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Hou S, Ye Z, Liao D, Bai L, Liu Y, Zhang J et al (2016) miR-23a, miR-146a and miR-301a confer predisposition to Vogt-Koyanagi-Harada syndrome but not to Behcet’s disease. Sci Rep 6:20057. doi: https://doi.org/10.1038/srep20057

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Yu H, Liu Y, Bai L, Kijlstra A, Yang P (2014) Predisposition to Behçet’s disease and VKH syndrome by genetic variants of miR-182. J Mol Med 92(9):961–967. doi: https://doi.org/10.1007/s00109-014-1159-9

    Article  CAS  PubMed  Google Scholar 

  14. Asakage M, Usui Y, Nezu N, Shimizu H, Tsubota K, Yamakawa N et al (2020) Comprehensive miRNA Analysis Using Serum From Patients With Noninfectious Uveitis. Investig Ophthalmol Vis Sci 61(11):4. doi: https://doi.org/10.1167/iovs.61.11.4

    Article  CAS  Google Scholar 

  15. Love MI, Huber W, Anders S (2014) Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol 15(12):550. doi: https://doi.org/10.1186/s13059-014-0550-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Jun M (2020) L. G. TCseq: time course sequencing data analysis. :1–8

  17. Ru Y, Kechris KJ, Tabakoff B, Hoffman P, Radcliffe RA, Bowler R et al (2014) The multiMiR R package and database: integration of microRNA-target interactions along with their disease and drug associations. Nucleic Acids Res 42(17):e133. doi: https://doi.org/10.1093/nar/gku631

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Kanehisa M, Goto S (2000) KEGG: kyoto encyclopedia of genes and genomes. Nucleic Acids Res 28(1):27–30. doi: https://doi.org/10.1093/nar/28.1.27

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Yu G, Wang LG, Han Y, He QY (2012) clusterProfiler: an R package for comparing biological themes among gene clusters. OMICS 16(5):284–287. doi: https://doi.org/10.1089/omi.2011.0118

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Wickham H (2016) ggplot2: Elegant Graphics for Data Analysis. Springer-Verlag, New York

    Book  Google Scholar 

  21. Schmittgen TD, Livak KJ (2008) Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc 3(6):1101–1108. doi: https://doi.org/10.1038/nprot.2008.73

    Article  CAS  PubMed  Google Scholar 

  22. Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D et al (2003) Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res 13(11):2498–2504. doi: https://doi.org/10.1101/gr.1239303

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Li JH, Liu S, Zhou H, Qu LH, Yang JH (2014) Nucleic Acids Res 42(Database issue):D92–D97. doi: https://doi.org/10.1093/nar/gkt1248. starBase v2.0: decoding miRNA-ceRNA, miRNA-ncRNA and protein-RNA interaction networks from large-scale CLIP-Seq data

  24. Karagkouni D, Paraskevopoulou MD, Tastsoglou S, Skoufos G, Karavangeli A, Pierros V et al (2020) DIANA-LncBase v3: indexing experimentally supported miRNA targets on non-coding transcripts. Nucleic Acids Res 48(D1):D101–d10. doi: https://doi.org/10.1093/nar/gkz1036

    Article  CAS  PubMed  Google Scholar 

  25. Obradovic D, Rommel KP, Blazek S, Klingel K, Gutberlet M, Lücke C et al (2021) The potential role of plasma miR-155 and miR-206 as circulatory biomarkers in inflammatory cardiomyopathy. ESC heart failure 8(3):1850–1860. doi: https://doi.org/10.1002/ehf2.13304

    Article  PubMed  PubMed Central  Google Scholar 

  26. Wright K, de Silva K, Plain KM, Purdie AC, Blair TA, Duggin IG et al (2021) Mycobacterial infection-induced miR-206 inhibits protective neutrophil recruitment via the CXCL12/CXCR4 signalling axis. PLoS Pathog 17(4):e1009186. doi: https://doi.org/10.1371/journal.ppat.1009186

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Hewitson JP, West KA, James KR, Rani GF, Dey N, Romano A et al (1950) Malat1 Suppresses Immunity to Infection through Promoting Expression of Maf and IL-10 in Th Cells. Journal of immunology (Baltimore, Md: 2020;204(11):2949-60. doi: https://doi.org/10.4049/jimmunol.1900940

  28. Pompura SL, Dominguez-Villar M (2018) The PI3K/AKT signaling pathway in regulatory T-cell development, stability, and function. J Leukoc Biol. doi: https://doi.org/10.1002/jlb.2mir0817-349r

    Article  PubMed  Google Scholar 

  29. Zhang Z, Yang X, Liu O, Cao X, Tong J, Xie T et al (2021) Differentially expressed microRNAs in peripheral blood mononuclear cells of non-segmental vitiligo and their clinical significance. J Clin Lab Anal 35(2):e23648. doi: https://doi.org/10.1002/jcla.23648

    Article  CAS  PubMed  Google Scholar 

  30. Shen Z, Sun J, Shao J, Xu J (2020) Ultraviolet B irradiation enhances the secretion of exosomes by human primary melanocytes and changes their exosomal miRNA profile. PLoS ONE 15(8):e0237023. doi: https://doi.org/10.1371/journal.pone.0237023

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Tessel MA, Benham AL, Krett NL, Rosen ST, Gunaratne PH (2011) Role for microRNAs in regulating glucocorticoid response and resistance in multiple myeloma. Horm cancer 2(3):182–189. doi: https://doi.org/10.1007/s12672-011-0072-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Bassili SS, Peyman GA, Gebhardt BM, Daun M, Ganiban GJ, Rifai A (1996) Detection of Epstein-Barr virus DNA by polymerase chain reaction in the vitreous from a patient with Vogt-Koyanagi-Harada syndrome. Retina (Philadelphia Pa) 16(2):160–161. doi: https://doi.org/10.1097/00006982-199616020-00013

    Article  CAS  PubMed  Google Scholar 

  33. Sugita S, Takase H, Kawaguchi T, Taguchi C, Mochizuki M (2007) Cross-reaction between tyrosinase peptides and cytomegalovirus antigen by T cells from patients with Vogt-Koyanagi-Harada disease. Int Ophthalmol 27(2–3):87–95. doi: https://doi.org/10.1007/s10792-006-9020-y

    Article  PubMed  Google Scholar 

  34. Sood AB, O’Keefe G, Bui D, Jain N (2019) Vogt-Koyanagi-Harada Disease Associated with Hepatitis B Vaccination. Ocul Immunol Inflamm 27(4):524–527. doi: https://doi.org/10.1080/09273948.2018.1483520

    Article  PubMed  Google Scholar 

  35. Dempsey PW, Doyle SE, He JQ, Cheng G (2003) The signaling adaptors and pathways activated by TNF superfamily. Cytokine Growth Factor Rev 14(3–4):193–209. doi: https://doi.org/10.1016/s1359-6101(03)00021-2

    Article  CAS  PubMed  Google Scholar 

  36. Shorning BY, Dass MS, Smalley MJ, Pearson HB (2020) The PI3K-AKT-mTOR Pathway and Prostate Cancer: At the Crossroads of AR, MAPK, and WNT Signaling. Int J Mol Sci 21(12). doi: https://doi.org/10.3390/ijms21124507

  37. Roux PP, Topisirovic I (2018) Signaling Pathways Involved in the Regulation of mRNA Translation. Mol Cell Biol 38(12). doi: https://doi.org/10.1128/mcb.00070-18

  38. Sabio G, Davis RJ (2014) TNF and MAP kinase signalling pathways. Semin Immunol 26(3):237–245. doi: https://doi.org/10.1016/j.smim.2014.02.009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Commodaro AG, Bombardieri CR, Peron JP, Saito KC, Guedes PM, Hamassaki DE et al (2010) p38{alpha} MAP kinase controls IL-17 synthesis in vogt-koyanagi-harada syndrome and experimental autoimmune uveitis. Investig Ophthalmol Vis Sci 51(7):3567–3574. doi: https://doi.org/10.1167/iovs.09-4393

    Article  Google Scholar 

  40. Wildner G, Kaufmann U (2013) What causes relapses of autoimmune diseases? The etiological role of autoreactive T cells. Autoimmun rev 12(11):1070–1075. doi: https://doi.org/10.1016/j.autrev.2013.04.001

    Article  CAS  PubMed  Google Scholar 

  41. Jia X, Li J, Shi D, Zhao Y, Dong Y, Ju H et al (2014) Grouping annotations on the subcellular layered interactome demonstrates enhanced autophagy activity in a recurrent experimental autoimmune uveitis T cell line. PLoS ONE 9(8):e104404. doi: https://doi.org/10.1371/journal.pone.0104404

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Liang L, Zhou Q, Feng L (2021) Decreased microRNA-155 in Behcet’s disease leads to defective control of autophagy thereby stimulating excessive proinflammatory cytokine production. Arthritis Res therapy 23(1):135. doi: https://doi.org/10.1186/s13075-021-02517-8

    Article  CAS  Google Scholar 

  43. Jeroudi A, Angeles-Han ST, Yeh S (2014) Efficacy of adalimumab for pediatric Vogt-Koyanagi-Harada syndrome. Opthalmic Surg Lasers Imaging Retin 45(4):332–334. doi: https://doi.org/10.3928/23258160-20140709-09

    Article  Google Scholar 

  44. Couto C, Schlaen A, Frick M, Khoury M, Lopez M, Hurtado E et al (2018) Adalimumab Treatment in Patients with Vogt-Koyanagi-Harada Disease. Ocul Immunol Inflamm 26(3):485–489. doi: https://doi.org/10.1080/09273948.2016.1236969

    Article  CAS  PubMed  Google Scholar 

  45. Su E, Oza VS, Latkany P (2019) A case of recalcitrant pediatric Vogt-Koyanagi-Harada disease successfully controlled with adalimumab. J Formos Med Association = Taiwan yi zhi 118(5):945–950. doi: https://doi.org/10.1016/j.jfma.2018.12.014

    Article  Google Scholar 

  46. Takayama K, Obata H, Takeuchi M (2020) Efficacy of Adalimumab for Chronic Vogt-Koyanagi-Harada Disease Refractory to Conventional Corticosteroids and Immunosuppressive Therapy and Complicated by Central Serous Chorioretinopathy. Ocul Immunol Inflamm 28(3):509–512. doi: https://doi.org/10.1080/09273948.2019.1603312

    Article  PubMed  Google Scholar 

  47. Abu El-Asrar AM, Berghmans N, Al-Obeidan SA, Gikandi PW, Opdenakker G, Van Damme J et al (2020) Soluble cytokine receptor levels in aqueous humour of patients with specific autoimmune uveitic entities: sCD30 is a biomarker of granulomatous uveitis. Eye 34(9):1614–1623. doi: https://doi.org/10.1038/s41433-019-0693-7

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

This work was supported by the grants from the National Natural Science Foundation of China (81671642 and 81870651), Tianjin Science and Technology Support Plan (20YFZCSY00990), Natural Science Foundation of Tianjin (20JCZDJC00100), Tianjin Key Medical Discipline (Specialty) Construction Project, the Science & Technology Development Fund of Tianjin Education Commission for Higher Education (2019ZD030), Tianjin Key Laboratory of Retinal Functions and Diseases (2019tjswmq004), and Tianjin Medical University Eye Hospital (TJLCZDXKQ006).

Author information

Authors and Affiliations

Authors

Contributions

Xiaomin Zhang conceived the study. Kailei Guo wrote the paper, Baiyi Li and Mi Zhang did the experiments, Fuhua Yang and Guixia Zhao revised the manuscript. All authors read and approved the final manuscript. And the authors thank Xinyi Zhang for guidance and assistance in sample collection.

Corresponding author

Correspondence to Xiaomin Zhang.

Ethics declarations

Competing Interests

The authors have no relevant financial or non-financial interests to disclose.

Ethics approval

The study was approved by the Local Ethics Research Committee of Tianjin Medical University Eye Hospital (No. 2016KY-14).

Consent to participate

All participants provided written informed consent before blood collection.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Kailei Guo, Baiyi Li, and Fuhua Yang contributed equally to this manuscript.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Guo, K., Li, B., Yang, F. et al. Different MicroRNA profiles in Peripheral Blood mononuclear cells from patients with initial-onset and recurrent vogt–Koyanagi–Harada Disease. Mol Biol Rep 49, 11421–11431 (2022). https://doi.org/10.1007/s11033-022-07753-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-022-07753-y

Keywords

Navigation