Skip to main content
SpringerLink
Log in

Circulating Levels of Hypoxia-regulating MicroRNAs in Systemic Lupus Erythematosus Patients with Hemolytic Anemia

  • Published:
Current Medical Science Aims and scope Submit manuscript

Abstract

Objective

MicroRNAs are fine regulators for gene expression during the post-transcriptional stage in many autoimmune diseases. HypoxamiRs (miR-210 and miR-21) play an important role in hypoxia and in inflammation-associated hypoxia. Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease that would potentiate many pathological complications, including hemolytic anemia. This study aimed to investigate the role of hypoxamiRs in SLE/hemolytic anemia patients.

Methods

This work was designed to analyze the circulating levels of↱ the miR-210 and miR-21 expressions and hypoxia-inducible factor-1α (HIF-α) in SLE/hemolytic anemia patients. SLE activity was evaluated for all patients by SLE Disease Activity Index (SLEDAI). Clinical manifestations/complications and serological/hematological investigations were reported. HIF-α concentration was assayed by ELISA and expression of miR-21 and miR-210 was analyzed by qRT-PCR.

Results

The results indicated that the fold change of the miR-210/miR-21 expressions in plasma was significantly elevated in SLE/hemolytic anemia patients. A strong positive correlation between the miR-210 and miR-21 expression levels was also recorded. Among the associated-disease complications, hypertension, arthritis, oral ulcers, and serositis were associated with a high circulating miR-210 expression, while the occurrence of renal disorders was associated with the increased miR-21 expression. Furthermore, the HIF-α level was remarkably elevated in SLE/hemolytic anemia patients. A high positive correlation was recorded between the HIF-α concentration and miR-210/miR-21 expression levels. The occurrence of oral ulcers, arthritis, and hypertension was associated with the increased HIF-α concentration. On the other hand, SLEDAI and white blood cell count were positively correlated with miR-21/ miR-210. The erythrocyte sedimentation rate was positively correlated with miR-21.

Conclusion

The dysregulation of the circulating miR-210/miR-210/HIF-1α levels in SLE/hemolytic anemia patients advocated that the hypoxia pathway might have an essential role in the pathogenesis and complications of these diseases.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Le X, Yu X, Shen N. Novel insights of microRNAs in the development of systemic lupus erythematosus. Curr Opin Rheumatol, 2017,29(5):450–457

    Article  Google Scholar 

  2. Banchereau R, Hong S, Cantarel B, et al. Personalized Immunomonitoring Uncovers Molecular Networks that Stratify Lupus Patients. Cell, 2016,165(3):551–565

    Article  Google Scholar 

  3. Pacheco-Lugo L, Sáenz-García J, Navarro Quiroz E, et al. Plasma cytokines as potential biomarkers of kidney damage in patients with systemic lupus erythematosus. Lupus, 2019,28(1):34–43

    Article  Google Scholar 

  4. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell, 2004,116(2):281–297

    Article  Google Scholar 

  5. Ambros V. The functions of animal microRNAs. Nature, 2004,431(7006):350–355

    Article  Google Scholar 

  6. Taganov KD, Boldin MP, Baltimore D. MicroRNAs and immunity: tiny players in a big field. Immunity, 2007,26(2):133–137

    Article  Google Scholar 

  7. Mehta A, Baltimore D. MicroRNAs as regulatory elements in immune system logic. Nat Rev Immunol, 2016,16(5):279–294

    Article  Google Scholar 

  8. Liu J, Qian C, Cao X. Post-Translational Modification Control of Innate Immunity. Immunity, 2016,45(1):15–30

    Article  Google Scholar 

  9. O’Connell RM, Rao DS, Baltimore D. microRNA regulation of inflammatory responses. Annu Rev Immunol, 2012,30:295–312

    Article  Google Scholar 

  10. Bracken CP, Scott HS, Goodall GJ. A network-biology perspective of microRNA function and dysfunction in cancer. Nat Rev Genet, 2016,17(12):719–732

    Article  Google Scholar 

  11. Leung AK, Sharp PA. MicroRNA functions in stress responses. Mol Cell, 2010,40(2):205–215

    Article  Google Scholar 

  12. Camps C, Buffa FM, Colella S, et al. hsa-miR-210 is induced by hypoxia and is an independent prognostic factor in breast cancer. Clin Cancer Res, 2008,14(5):1340–1348

    Article  Google Scholar 

  13. Giannakakis A, Sandaltzopoulos R, Greshock J, et al. miR-210 links hypoxia with cell cycle regulation and is deleted in human epithelial ovarian cancer. Cancer Biol Ther, 2008,7(2):255–264

    Article  Google Scholar 

  14. Chan YC, Banerjee J, Choi SY, et al. miR-210: the master hypoxamir. Microcirculation, 2012,19(3):215–223

    Article  Google Scholar 

  15. Huang X, Le QT, Giaccia AJ. MiR-210—micromanager of the hypoxia pathway. Trends Mol Med, 2010,16(5):230–237

    Article  Google Scholar 

  16. Eltzschig HK, Carmeliet P. Hypoxia and inflammation. N Engl J Med, 2011,364(7):656–665

    Article  Google Scholar 

  17. Wang H, Flach H, Onizawa M, et al. Negative regulation of Hif1a expression and TH17 differentiation by the hypoxia-regulated microRNA miR-210. Nat Immunol, 2014,15(4):393–401

    Article  Google Scholar 

  18. Dang EV, Barbi J, Yang HY, et al. Control of T(H)17/T(reg) balance by hypoxia-inducible factor 1. Cell, 2011,146(5):772–784

    Article  Google Scholar 

  19. Crowther M, Podolak-Dawidziak M. Hemolytic Anemia: General Considerations. McMaster Textbook of Internal Medicine. Kraków: Medycyna Praktyczna. 2020

  20. Tan EM, Cohen AS, Fries JF, et al. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum, 1982,25(11):1271–1277

    Article  Google Scholar 

  21. Bombardier C, Gladman DD, Urowitz MB, et al. Derivation of the SLEDAI. A disease activity index for lupus patients. The Committee on Prognosis Studies in SLE. Arthritis Rheum, 1992,35(6):630–640

    Article  Google Scholar 

  22. Chun HY, Chung JW, Kim HA, et al. Cytokine IL-6 and IL-10 as biomarkers in systemic lupus erythematosus. J Clin Immunol, 2007,27(5):461–466

    Article  Google Scholar 

  23. Mok MY, Wu HJ, Lo Y, et al. The relation of interleukin 17 (IL-17) and IL-23 to Th1/Th2 cytokines and disease activity in systemic lupus erythematosus. J Rheumatol, 2010,37(10):2046–2052

    Article  Google Scholar 

  24. World Medical Association. World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA, 2013,310(20):2191–2194

    Article  Google Scholar 

  25. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods, 2001,25(4):402–408

    Article  Google Scholar 

  26. Wu YH, Chan YF, Hsieh HL, et al. Upregulation of miR-210-5p in Systemic Lupus Erythematosus Impairs Silent Clearance of Dead Cell Remnants. FASEB J, 2020,34(S1), Supplement: Experimental Biology, Meeting Abstracts, Pages 1–1.

    Google Scholar 

  27. Huang Q, Chen SS, Li J, et al. miR-210 expression in PBMCs from patients with systemic lupus erythematosus and rheumatoid arthritis. Ir J Med Sci, 2018,187(1):243–249

    Article  Google Scholar 

  28. Dai Y, Huang YS, Tang M, et al. Microarray analysis of microRNA expression in peripheral blood cells of systemic lupus erythematosus patients. Lupus, 2007,16(12):939–946

    Article  Google Scholar 

  29. Higgins DF, Kimura K, Bernhardt WM, et al. Hypoxia promotes fibrogenesis in vivo via HIF-1 stimulation of epithelial-to-mesenchymal transition. J Clin Invest, 2007,117(12):3810–3820

    Google Scholar 

  30. Kimura K, Iwano M, Higgins DF, et al. Stable expression of HIF-1alpha in tubular epithelial cells promotes interstitial fibrosis. Am J Physiol Renal Physiol, 2008,295(4):F1023–1029

    Article  Google Scholar 

  31. Ma C, Wei J, Zhan F, et al. Urinary hypoxia-inducible factor-1alpha levels are associated with histologic chronicity changes and renal function in patients with lupus nephritis. Yonsei Med J, 2012,53(3):587–592

    Article  Google Scholar 

  32. Deng W, Ren Y, Feng X, et al. Hypoxia inducible factor-1 alpha promotes mesangial cell proliferation in lupus nephritis. Am J Nephrol, 2014,40(6):507–515

    Article  Google Scholar 

  33. Garchow B, Maque Acosta Y, et al. HIF-1α and miR-210 differential and lineage-specific expression in systemic lupus erythematosus. Mol Immunol, 2021,133:128–134

    Article  Google Scholar 

  34. Rigó J, Molvarec A, Nagy B, et al. Expression analysis of circulating exosomal hsa-miR-210 in hypertensive disorders of pregnancy: Biomarkers, prediction of preeclampsia. Pregnancy Hypertens, 2016,6(3):183

    Article  Google Scholar 

Download references

Acknowledgment

This work was supported by the Taif University Researchers Supporting Project (No. TURSP-2020/103).

Author information

Authors and Affiliations

  1. Clinical Laboratory Sciences Department, College of Applied Medical Sciences, Taif University, Taif, 21944, Saudi Arabia

    Amira M. Gamal-Eldeen

  2. High Altitude Research Center, Prince Sultan Medical Complex, Al-Hawiyah, Taif University, Taif, 21944, Saudi Arabia

    Amira M. Gamal-Eldeen & Fayez Althobaiti

  3. Cancer Biology and Genetics Laboratory, Centre of Excellence for Advanced Sciences, National Research Centre, Cairo, 12622, Egypt

    Cinderella A. Fahmy

  4. Biochemistry Department, National Research Centre, Cairo, 12622, Egypt

    Cinderella A. Fahmy

  5. Radiological Sciences Department, College of Applied Medical Sciences, Taif University, Taif, 21944, Saudi Arabia

    Bassem M. Raafat

  6. Biotechnology Department, Faculty of Science, Taif University, Taif, 21944, Saudi Arabia

    Fayez Althobaiti

  7. Department of Rheumatology and Rehabilitation, Faculty of Medicine, Cairo University, El-Kasr El-Aini Hospital, Cairo, 12613, Egypt

    Iman H. Bassyouni

  8. Molecular Biology Department, Genetic Engineering and Biotechnology Research Institute (GEBRI), Sadat City University, Sadat City, 32897, Egypt

    Roba M. Talaat

Authors
  1. Amira M. Gamal-Eldeen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Cinderella A. Fahmy
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bassem M. Raafat
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Fayez Althobaiti
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Iman H. Bassyouni
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Roba M. Talaat
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Amira M. Gamal-Eldeen.

Ethics declarations

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gamal-Eldeen, A.M., Fahmy, C.A., Raafat, B.M. et al. Circulating Levels of Hypoxia-regulating MicroRNAs in Systemic Lupus Erythematosus Patients with Hemolytic Anemia. CURR MED SCI 42, 1231–1239 (2022). https://doi.org/10.1007/s11596-022-2644-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11596-022-2644-y

Key words

Search

Navigation