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The role of microRNAs in skin fibrosis

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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.

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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

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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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Authors and Affiliations

  1. Department of Dermatology, University of California Davis, 3301 C Street, Sacramento, CA, 95816, USA

    Olubukola Babalola, Andrew Mamalis, Hadar Lev-Tov & Jared Jagdeo

  2. Dermatology Service, Sacramento VA Medical Center, Mather, CA, 95655, USA

    Olubukola Babalola, Andrew Mamalis, Hadar Lev-Tov & Jared Jagdeo

  3. Department of Dermatology, Albert Einstein School of Medicine, Bronx, NY, 10461, USA

    Hadar Lev-Tov

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  2. Andrew Mamalis
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  3. Hadar Lev-Tov
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  4. Jared Jagdeo
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Corresponding author

Correspondence to Jared Jagdeo.

Additional information

O. Babalola and A. Mamalis contributed equally to the preparation of this manuscript.

The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Babalola, O., Mamalis, A., Lev-Tov, H. et al. The role of microRNAs in skin fibrosis. Arch Dermatol Res 305, 763–776 (2013). https://doi.org/10.1007/s00403-013-1410-1

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  • DOI: https://doi.org/10.1007/s00403-013-1410-1

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