Skip to main content

Advertisement

Log in

MicroRNA Expression Abnormalities in Limited Cutaneous Scleroderma and Diffuse Cutaneous Scleroderma

  • Published:
Journal of Clinical Immunology Aims and scope Submit manuscript

Abstract

Scleroderma (systemic sclerosis, SSc) is a complex autoimmune disease caused by progressive fibrotic replacement of normal tissue architecture, a progressive and ultimately fatal process that currently has no cure. Although dysregulation of microRNAs (miRNAs) is known to be involved in a variety of pathophysiologic processes, the role of miRNAs in SSc is unclear. In comparison with the normal skin tissues, miRNAs were aberrantly expressed in limited cutaneous scleroderma and diffuse cutaneous scleroderma skin tissues. We also identified miRNAs whose expressions were correlated with SSc fibrosis: miR-21, miR-31, miR-146, miR-503, miR-145, and miR-29b were predicted to be involved. This study further confirmed that miR-21 was increased whereas miR-145 and miR-29b were decreased both in the skin tissues and fibroblasts. As predicted target genes, SMAD7, SAMD3, and COL1A1 were regulated by these miRNAs. After stimulation with transforming growth factor β, the expression of miR-21 was increased and that of SMAD7 mRNA was decreased. MiR-145 was upregulated whereas the mRNA level of SMAD3 was downregulated. The downregulation of miR-29b was correlated with the upregulation of COL1A1 mRNA. MiRNAs might play an important role in the pathogenesis of SSc and suggest a potential therapy.

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.

Institutional subscriptions

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

Similar content being viewed by others

References

  1. Gabrielli A, Avvedimento EV, Krieg T. Scleroderma. N Engl J Med. 2009;360(19):1989–2003.

    Article  PubMed  CAS  Google Scholar 

  2. LeRoy EC, Black C, Fleischmajer R, Jablonska S, Krieg T, Medsger Jr TA, et al. Scleroderma (systemic sclerosis): classification, subsets and pathogenesis. J Rheumatol. 1988;15(2):202–5.

    PubMed  CAS  Google Scholar 

  3. Varga J, Abraham D. Systemic sclerosis: a prototypic multisystem fibrotic disorder. J Clin Invest. 2007;117(3):557–67.

    Article  PubMed  CAS  Google Scholar 

  4. Blobe GC, Schiemann WP, Lodish HF. Role of transforming growth factor beta in human disease. N Engl J Med. 2000;342(18):1350–8.

    Article  PubMed  CAS  Google Scholar 

  5. Leask A, Abraham DJ, Finlay DR, Holmes A, Pennington D, Shi-Wen X, et al. Dysregulation of transforming growth factor beta signaling in scleroderma: overexpression of endoglin in cutaneous scleroderma fibroblasts. Arthritis Rheum. 2002;46(7):1857–65.

    Article  PubMed  CAS  Google Scholar 

  6. Gabrielli A, Di Loreto C, Taborro R, Candela M, Sambo P, Nitti C, et al. Immunohistochemical localization of intracellular and extracellular associated TGF beta in the skin of patients with systemic sclerosis (scleroderma) and primary Raynaud’s phenomenon. Clin Immunol Immunopathol. 1993;68(3):340–9.

    Article  PubMed  CAS  Google Scholar 

  7. Sfikakis PP, McCune BK, Tsokos M, Aroni K, Vayiopoulos G, Tsokos GC. Immunohistological demonstration of transforming growth factor-beta isoforms in the skin of patients with systemic sclerosis. Clin Immunol Immunopathol. 1993;69(2):199–204.

    Article  PubMed  CAS  Google Scholar 

  8. Xu WD, Leroy EC, Smith EA. Fibronectin release by systemic sclerosis and normal dermal fibroblasts in response to TGF-beta. J Rheumatol. 1991;18(2):241–6.

    PubMed  CAS  Google Scholar 

  9. Varga J. Scleroderma and Smads: dysfunctional Smad family dynamics culminating in fibrosis. Arthritis Rheum. 2002;46(7):1703–13.

    Article  PubMed  CAS  Google Scholar 

  10. O’Connell RM, Rao DS, Chaudhuri AA, Baltimore D. Physiological and pathological roles for microRNAs in the immune system. Nat Rev Immunol. 2010;10(2):111–22.

    Article  PubMed  Google Scholar 

  11. Stefani G, Slack FJ. Small non-coding RNAs in animal development. Nat Rev Mol Cell Biol. 2008;9(3):219–30.

    Article  PubMed  CAS  Google Scholar 

  12. Bushati N, Cohen SM. microRNA functions. Annu Rev Cell Dev Biol. 2007;23:175–205.

    Article  PubMed  CAS  Google Scholar 

  13. Jiang X, Tsitsiou E, Herrick SE, Lindsay MA. MicroRNAs and the regulation of fibrosis. FEBS J. 2010;277(9):2015–21.

    Article  PubMed  CAS  Google Scholar 

  14. Li H, Yang R, Fan X, Gu T, Zhao Z, Chang D, et al. MicroRNA array analysis of microRNAs related to systemic scleroderma. Rheumatol Int. 2010;32(2):307–13.

    Google Scholar 

  15. Maurer B, Stanczyk J, Jungel A, Akhmetshina A, Trenkmann M, Brock M, et al. MicroRNA-29, a key regulator of collagen expression in systemic sclerosis. Arthritis Rheum. 2010;62(6):1733–43.

    Article  PubMed  CAS  Google Scholar 

  16. Masi AT. Preliminary criteria for the classification of systemic sclerosis (scleroderma). Subcommittee for scleroderma criteria of the American Rheumatism Association Diagnostic and Therapeutic Criteria Committee. Arthritis Rheum. 1980;23(5):581–90.

    Article  Google Scholar 

  17. Sargent JL, Milano A, Bhattacharyya S, Varga J, Connolly MK, Chang HY, et al. A TGFbeta-responsive gene signature is associated with a subset of diffuse scleroderma with increased disease severity. J Invest Dermatol. 2010;130(3):694–705.

    Article  PubMed  CAS  Google Scholar 

  18. Wynn TA. Cellular and molecular mechanisms of fibrosis. J Pathol. 2008;214(2):199–210.

    Article  PubMed  CAS  Google Scholar 

  19. Brown BD, Naldini L. Exploiting and antagonizing microRNA regulation for therapeutic and experimental applications. Nat Rev Genet. 2009;10(8):578–85.

    Article  PubMed  CAS  Google Scholar 

  20. van Rooij E, Marshall WS, Olson EN. Toward microRNA-based therapeutics for heart disease: the sense in antisense. Circ Res. 2008;103(9):919–28.

    Article  PubMed  Google Scholar 

  21. Elmen J, Lindow M, Schutz S, Lawrence M, Petri A, Obad S, et al. LNA-mediated microRNA silencing in non-human primates. Nature. 2008;452(7189):896–9.

    Article  PubMed  CAS  Google Scholar 

  22. Elmen J, Lindow M, Silahtaroglu A, Bak M, Christensen M, Lind-Thomsen A, et al. Antagonism of microRNA-122 in mice by systemically administered LNA-antimiR leads to up-regulation of a large set of predicted target mRNAs in the liver. Nucleic Acids Res. 2008;36(4):1153–62.

    Article  PubMed  CAS  Google Scholar 

  23. Esau C, Davis S, Murray SF, Yu XX, Pandey SK, Pear M, et al. miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting. Cell Metab. 2006;3(2):87–98.

    Article  PubMed  CAS  Google Scholar 

  24. Kawashita Y, Jinnin M, Makino T, Kajihara I, Makino K, Honda N, et al. Circulating miR-29a levels in patients with scleroderma spectrum disorder. J Dermatol Sci. 2011;61(1):67–9.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by grants from National Natural Science Foundation of China (30671947, 30900588) and Graduate Research Innovation Fund of Hunan Province (no. CX2011B061).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Xiaoxia Zuo.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhu, H., Li, Y., Qu, S. et al. MicroRNA Expression Abnormalities in Limited Cutaneous Scleroderma and Diffuse Cutaneous Scleroderma. J Clin Immunol 32, 514–522 (2012). https://doi.org/10.1007/s10875-011-9647-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10875-011-9647-y

Keywords

Navigation