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Archives of Dermatological Research

, Volume 305, Issue 9, pp 763–776 | Cite as

The role of microRNAs in skin fibrosis

  • Olubukola Babalola
  • Andrew Mamalis
  • Hadar Lev-Tov
  • Jared Jagdeo
Review Article

Abstract

Fibrotic skin disorders may be debilitating and impair quality of life. There are few effective treatment options for cutaneous fibrotic diseases. In this review, we discuss our current understanding of the role of microRNAs (miRNAs) in skin fibrosis. miRNAs are a class of small, non-coding RNAs involved in skin fibrosis. These small RNAs range from 18 to 25 nucleotides in length and modify gene expression by binding to target messenger RNA (mRNA), causing degradation of the target mRNA or inhibiting the translation into proteins. We present an overview of the biogenesis, maturation and function of miRNAs. We highlight miRNA’s role in key skin fibrotic processes including: transforming growth factor-beta signaling, extracellular matrix deposition, and fibroblast proliferation and differentiation. Some miRNAs are profibrotic and their upregulation favors these processes contributing to fibrosis, while anti-fibrotic miRNAs inhibit these processes and may be reduced in fibrosis. Finally, we describe the diagnostic and therapeutic significance of miRNAs in the management of skin fibrosis. The discovery that miRNAs are detectable in serum, plasma, and other bodily fluids, and are relatively stable, suggests that miRNAs may serve as valuable biomarkers to monitor disease progression and response to treatment. In the treatment of skin fibrosis, anti-fibrotic miRNAs may be upregulated using mimics and viral vectors. Conversely, profibrotic miRNAs may be downregulated by employing anti-miRNAs, sponges, erasers and masks. We believe that miRNA-based therapies hold promise as important treatments and may transform the management of fibrotic skin diseases by physicians.

Keywords

Skin fibrosis MicroRNA miRNA Collagen Therapeutics 

Abbreviations

Ago

Argonuate

AAV

Adeno-associated viral vector

AV

Adenoviral vector

CTGF

Connective tissue growth factor

ECM

Extracellular matrix

EMT

Epithelial-to-mesenchymal transition or transformation

ERK

Extracellular receptor kinase

IL

Interleukin

LNA

Locked nucleic acid

LV

Lentiviral vector

miRNA

MicroRNA

MMP

Matrix metalloproteinase

mRNA

Messenger RNA

MAPK

Mitogen-activated protein kinase

MRSS

Modified Rodnan skin score

NF-κΒ

Nuclear factor-kappa B

PDGF

Platelet-derived growth factor

pre-miRNA

Precursor-miRNA

pri-miRNA

Primary-miRNA

PTEN

Phosphatase and tensin homolog

RISC

RNA-induced silencing complex

SMA

Smooth muscle actin

TGF

Transforming growth factor

UTR

Untranslated region

Notes

Acknowledgments

The project described was supported by the National Center for Advancing Translational Sciences, National Institutes of Health, through grant number UL1 TR000002 and linked award TL1 TR000133 and KL2 TR000134. Research reported in this publication was supported by the National Institute Of Allergy And Infectious Diseases of the National Institutes of Health under Award Number R33AI080604.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Olubukola Babalola
    • 1
    • 2
  • Andrew Mamalis
    • 1
    • 2
  • Hadar Lev-Tov
    • 1
    • 2
    • 3
  • Jared Jagdeo
    • 1
    • 2
  1. 1.Department of DermatologyUniversity of California DavisSacramentoUSA
  2. 2.Dermatology ServiceSacramento VA Medical CenterMatherUSA
  3. 3.Department of DermatologyAlbert Einstein School of MedicineBronxUSA

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