title: The role of microRNAs in skin fibrosis.
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, antifibrotic 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.
authors.forename: Olubukola
authors.initials: O
authors.lastname: Babalola
authors.forename: Andrew
authors.initials: A
authors.lastname: Mamalis
authors.forename: Hadar
authors.initials: H
authors.lastname: Lev-Tov
authors.forename: Jared
authors.initials: J
authors.lastname: Jagdeo
mesh_terms: D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation; D006801:Humans; D007627:Keloid / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D035683:MicroRNAs / Q000235:genetics*; D009841:Oligonucleotides / Q000627:therapeutic use; D012595:Scleroderma, Systemic / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D012867:Skin / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D035683:MicroRNAs; D009841:Oligonucleotides; D016212:Transforming Growth Factor beta; C581159:miravirsen
references.citation: Open Rheumatol J. 2012;6:130-9
references.pmid: 22802911
references.citation: J Cell Biol. 2012 Oct 29;199(3):407-12
references.pmid: 23109665
references.citation: Biochem Biophys Res Commun. 2009 Feb 13;379(3):790-4
references.pmid: 19126397
references.citation: J Dermatol Sci. 2009 Mar;53(3):169-75
references.pmid: 19058951
references.citation: Arch Dermatol Res. 2013 Jan;305(1):1-8
references.pmid: 23208311
references.citation: Future Oncol. 2007 Oct;3(5):521-37
references.pmid: 17927518
references.citation: ScientificWorldJournal. 2012;2012:252457
references.pmid: 22623890
references.citation: Cell. 2009 Jan 23;136(2):215-33
references.pmid: 19167326
references.citation: Cell Res. 2008 Oct;18(10):997-1006
references.pmid: 18766170
references.citation: Curr Hypertens Rep. 2012 Feb;14(1):79-87
references.pmid: 22052337
references.citation: Br J Dermatol. 2012 Jan;166(1):22-8
references.pmid: 21824129
references.citation: Methods Mol Biol. 2013;936:343-56
references.pmid: 23007520
references.citation: Curr Opin Rheumatol. 2004 Nov;16(6):733-8
references.pmid: 15577612
references.citation: Nature. 2008 Dec 18;456(7224):980-4
references.pmid: 19043405
references.citation: Cancer Res. 2007 Apr 1;67(7):2912-5
references.pmid: 17409393
references.citation: FEBS J. 2010 May;277(9):2015-21
references.pmid: 20412055
references.citation: Rejuvenation Res. 2011 Feb;14(1):57-66
references.pmid: 21329452
references.citation: J Burn Care Rehabil. 2001 Nov-Dec;22(6):401-5
references.pmid: 11761392
references.citation: Expert Opin Ther Targets. 2012 Sep;16(9):875-9
references.pmid: 22793265
references.citation: PLoS One. 2008 Sep 05;3(9):e3148
references.pmid: 18773077
references.citation: Clin Exp Dermatol. 2008 May;33(3):312-5
references.pmid: 18419608
references.citation: Arch Dermatol Res. 2013 Jan;305(1):9-15
references.pmid: 22965811
references.citation: Proc Natl Acad Sci U S A. 2006 Jun 13;103(24):9136-41
references.pmid: 16754881
references.citation: Curr Anesthesiol Rep. 2013 Mar 1;1(1):63-70
references.pmid: 23524956
references.citation: Arthritis Rheum. 2010 Jun;62(6):1733-43
references.pmid: 20201077
references.citation: J Trauma. 1983 Nov;23(11):1001-4
references.pmid: 6355500
references.citation: Am J Pathol. 2012 Feb;180(2):703-14
references.pmid: 22142808
references.citation: Gen Hosp Psychiatry. 2007 Jan-Feb;29(1):14-20
references.pmid: 17189739
references.citation: J Clin Immunol. 2012 Jun;32(3):514-22
references.pmid: 22307526
references.citation: Curr Opin Rheumatol. 2013 Jan;25(1):71-7
references.pmid: 23114586
references.citation: Am J Med Sci. 2013 Aug;346(2):98-103
references.pmid: 23221517
references.citation: Nucleic Acids Res. 2013 Apr 1;41(6):3833-44
references.pmid: 23396279
references.citation: Curr Opin Nephrol Hypertens. 2012 Jul;21(4):410-6
references.pmid: 22622653
references.citation: Rheumatology (Oxford). 2012 Sep;51(9):1550-6
references.pmid: 22661558
references.citation: Lasers Surg Med. 2012 Sep;44(7):517-24
references.pmid: 22907286
references.citation: Proc Natl Acad Sci U S A. 1991 Feb 15;88(4):1330-4
references.pmid: 1847517
references.citation: J Dermatol Sci. 2011 Jan;61(1):67-9
references.pmid: 21129921
references.citation: Am J Pathol. 2013 Jan;182(1):206-16
references.pmid: 23159943
references.citation: J Burn Care Rehabil. 1994 Mar-Apr;15(2):164-8
references.pmid: 8195258
references.citation: J Psychosom Res. 2008 Feb;64(2):205-12
references.pmid: 18222134
references.citation: Science. 2010 Jan 8;327(5962):198-201
references.pmid: 19965718
references.citation: Pharmacol Ther. 2010 Jan;125(1):92-104
references.pmid: 19896977
references.citation: J Am Heart Assoc. 2013 Apr 23;2(2):e000078
references.pmid: 23612897
references.citation: Mol Ther. 2004 Jan;9(1):93-100
references.pmid: 14741782
references.citation: J Immunol. 2012 Apr 1;188(7):3323-31
references.pmid: 22379029
references.citation: Exp Dermatol. 2011 Feb;20(2):119-24
references.pmid: 21255090
references.citation: PLoS One. 2007 Jul 11;2(7):e610
references.pmid: 17622355
references.citation: Physiol Res. 2012;61(4):337-46
references.pmid: 22670697
references.citation: Autoimmun Rev. 2011 Mar;10(5):267-75
references.pmid: 20863909
references.citation: J Immunol. 2013 Apr 15;190(8):3905-15
references.pmid: 23509348
references.citation: RNA Biol. 2011 Sep-Oct;8(5):706-13
references.pmid: 21712654
references.citation: Tohoku J Exp Med. 2010 Jul;221(3):203-9
references.pmid: 20543536
references.citation: Rheumatol Int. 2012 Feb;32(2):307-13
references.pmid: 21052672
references.citation: Aesthetic Plast Surg. 2012 Feb;36(1):193-201
references.pmid: 21701945
references.citation: Cell. 2009 Jun 12;137(6):1032-46
references.pmid: 19524507
references.citation: J Invest Dermatol. 2012 Jun;132(6):1597-604
references.pmid: 22358059
references.citation: Am J Physiol Renal Physiol. 2013 May 15;304(10):F1266-73
references.pmid: 23408168
references.citation: J Biol Chem. 2012 Aug 24;287(35):29324-35
references.pmid: 22773832
references.citation: Clin Exp Dermatol. 2012 Jan;37(1):34-9
references.pmid: 21883400
references.citation: J Pathol. 2013 Jan;229(2):274-85
references.pmid: 23042530
references.citation: J Clin Immunol. 2013 Aug;33(6):1100-9
references.pmid: 23657402
references.citation: Proc Natl Acad Sci U S A. 2008 Jul 29;105(30):10513-8
references.pmid: 18663219
references.citation: J Cell Physiol. 2007 Aug;212(2):285-92
references.pmid: 17516552
references.citation: Cell. 2004 Jan 23;116(2):281-97
references.pmid: 14744438
references.citation: Mol Biol Cell. 2008 Aug;19(8):3272-82
references.pmid: 18508928
references.citation: Proc Natl Acad Sci U S A. 2009 Nov 3;106(44):18704-9
references.pmid: 19843690
references.citation: PLoS One. 2008;3(11):e3694
references.pmid: 19002258
references.citation: J Invest Dermatol. 2011 Oct;131(10):1996-2003
references.pmid: 21654839
references.citation: Am J Pathol. 2012 Dec;181(6):1911-20
references.pmid: 23159215
references.citation: Cell Mol Life Sci. 2013 Apr;70(7):1149-69
references.pmid: 22983383
references.citation: J Cutan Pathol. 2009 May;36(5):607-10
references.pmid: 19476539
references.citation: Expert Opin Biol Ther. 2004 Sep;4(9):1373-86
references.pmid: 15335305
references.citation: Curr Opin Cell Biol. 2013 Apr;25(2):200-7
references.pmid: 23434068
references.citation: Nat Med. 2012 Jul 06;18(7):1028-40
references.pmid: 22772564
references.citation: Adv Exp Med Biol. 2013;768:45-59
references.pmid: 23224964
references.citation: Arch Dermatol Res. 2012 Apr;304(3):195-202
references.pmid: 21968601
references.citation: Semin Cancer Biol. 2008 Apr;18(2):111-22
references.pmid: 18296065