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


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.


Skin fibrosis MicroRNA miRNA Collagen Therapeutics 





Adeno-associated viral vector


Adenoviral vector


Connective tissue growth factor


Extracellular matrix


Epithelial-to-mesenchymal transition or transformation


Extracellular receptor kinase




Locked nucleic acid


Lentiviral vector




Matrix metalloproteinase


Messenger RNA


Mitogen-activated protein kinase


Modified Rodnan skin score


Nuclear factor-kappa B


Platelet-derived growth factor






Phosphatase and tensin homolog


RNA-induced silencing complex


Smooth muscle actin


Transforming growth factor


Untranslated region



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.


  1. 1.
    Abdullah A, Blakeney P, Hunt R, Broemeling L, Phillips L, Herndon DN, Robson MC (1994) Visible scars and self-esteem in pediatric patients with burns. J Burn Care Rehabil 15(2):164–168PubMedCrossRefGoogle Scholar
  2. 2.
    Bader A, Lorenz K, Richter A, Scheffler K, Kern L, Ebert S, Giri S, Behrens M, Dornseifer U, Macchiarini P, Machens HG (2011) Interactive role of trauma cytokines and erythropoietin and their therapeutic potential for acute and chronic wounds. Rejuvenation Res 14(1):57–66. doi: 10.1089/rej.2010.1050 PubMedCrossRefGoogle Scholar
  3. 3.
    Banerjee J, Sen CK (2013) MicroRNAs in skin and wound healing. Methods Mol Biol 936:343–356. doi: 10.1007/978-1-62703-083-0_26 PubMedCrossRefGoogle Scholar
  4. 4.
    Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116(2):281–297PubMedCrossRefGoogle Scholar
  5. 5.
    Bartel DP (2009) MicroRNAs: target recognition and regulatory functions. Cell 136(2):215–233. doi: 10.1016/j.cell.2009.01.002 PubMedCrossRefGoogle Scholar
  6. 6.
    Batkai S, Thum T (2012) MicroRNAs in hypertension: mechanisms and therapeutic targets. Curr Hypertens Rep 14(1):79–87. doi: 10.1007/s11906-011-0235-6 PubMedCrossRefGoogle Scholar
  7. 7.
    Bolognia JL, Jorizzo JL, Schaffer JV (2012) Dermatology, 3rd edn. Mosby, St. LouisGoogle Scholar
  8. 8.
    Bowen T, Jenkins RH, Fraser DJ (2013) MicroRNAs, transforming growth factor beta-1, and tissue fibrosis. J Pathol 229(2):274–285. doi: 10.1002/path.4119 PubMedCrossRefGoogle Scholar
  9. 9.
    Brych SB, Engrav LH, Rivara FP, Ptacek JT, Lezotte DC, Esselman PC, Kowalske KJ, Gibran NS (2001) Time off work and return to work rates after burns: systematic review of the literature and a large two-center series. J Burn Care Rehabil 22(6):401–405PubMedCrossRefGoogle Scholar
  10. 10.
    Chen X, Ba Y, Ma L, Cai X, Yin Y, Wang K, Guo J, Zhang Y, Chen J, Guo X, Li Q, Li X, Wang W, Zhang Y, Wang J, Jiang X, Xiang Y, Xu C, Zheng P, Zhang J, Li R, Zhang H, Shang X, Gong T, Ning G, Wang J, Zen K, Zhang J, Zhang CY (2008) Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res 18(10):997–1006. doi: 10.1038/cr.2008.282 PubMedCrossRefGoogle Scholar
  11. 11.
    Cheng J, Wang Y, Wang D, Wu Y (2013) Identification of collagen 1 as a post-transcriptional target of miR-29b in skin fibroblasts: therapeutic implication for scar reduction. Am J Med Sci 346(2):98–103. doi: 10.1097/MAJ.0b013e318267680d PubMedCrossRefGoogle Scholar
  12. 12.
    Cheng J, Yu H, Deng S, Shen G (2010) MicroRNA profiling in mid- and late-gestational fetal skin: implication for scarless wound healing. Tohoku J Exp Med 221(3):203–209PubMedCrossRefGoogle Scholar
  13. 13.
    Eming SA, Krieg T, Davidson JM (2004) Gene transfer in tissue repair: status, challenges and future directions. Expert Opin Biol Ther 4(9):1373–1386. doi: 10.1517/14712598.4.9.1373 PubMedCrossRefGoogle Scholar
  14. 14.
    Engrav LH, Heimbach DM, Reus JL, Harnar TJ, Marvin JA (1983) Early excision and grafting vs. nonoperative treatment of burns of indeterminant depth: a randomized prospective study. J Trauma 23(11):1001–1004PubMedCrossRefGoogle Scholar
  15. 15.
    Etoh M, Jinnin M, Makino K, Yamane K, Nakayama W, Aoi J, Honda N, Kajihara I, Makino T, Fukushima S, Ihn H (2013) microRNA-7 down-regulation mediates excessive collagen expression in localized scleroderma. Arch Dermatol Res 305(1):9–15. doi: 10.1007/s00403-012-1287-4 PubMedCrossRefGoogle Scholar
  16. 16.
    Falanga V, Iwamoto S (2012) Mechanisms of wound repair, wound healing, and wound dressing. In: Fitzpatrick’s dermatology in general medicine, 8th edn. McGraw-Hill, New YorkGoogle Scholar
  17. 17.
    Fasanaro P, Greco S, Ivan M, Capogrossi MC, Martelli F (2010) microRNA: emerging therapeutic targets in acute ischemic diseases. Pharmacol Ther 125(1):92–104. doi: 10.1016/j.pharmthera.2009.10.003 PubMedCrossRefGoogle Scholar
  18. 18.
    Gilad S, Meiri E, Yogev Y, Benjamin S, Lebanony D, Yerushalmi N, Benjamin H, Kushnir M, Cholakh H, Melamed N, Bentwich Z, Hod M, Goren Y, Chajut A (2008) Serum microRNAs are promising novel biomarkers. PLoS ONE 3(9):e3148. doi: 10.1371/journal.pone.0003148 PubMedCrossRefGoogle Scholar
  19. 19.
    Guo Y, Xiao L, Sun L, Liu F (2012) Wnt/beta-catenin signaling: a promising new target for fibrosis diseases. Physiol Res (Acad Sci Bohemoslov) 61(4):337–346Google Scholar
  20. 20.
    Honda N, Jinnin M, Kajihara I, Makino T, Makino K, Masuguchi S, Fukushima S, Okamoto Y, Hasegawa M, Fujimoto M, Ihn H (2012) TGF-beta-mediated downregulation of microRNA-196a contributes to the constitutive upregulated type I collagen expression in scleroderma dermal fibroblasts. J Immunol 188(7):3323–3331. doi: 10.4049/jimmunol.1100876 PubMedCrossRefGoogle Scholar
  21. 21.
    Honda N, Jinnin M, Kira-Etoh T, Makino K, Kajihara I, Makino T, Fukushima S, Inoue Y, Okamoto Y, Hasegawa M, Fujimoto M, Ihn H (2013) miR-150 down-regulation contributes to the constitutive type I collagen overexpression in scleroderma dermal fibroblasts via the induction of integrin beta3. Am J Pathol 182(1):206–216. doi: 10.1016/j.ajpath.2012.09.023 PubMedCrossRefGoogle Scholar
  22. 22.
    Hu B, Phan SH (2013) Myofibroblasts. Curr Opin Rheumatol 25(1):71–77. doi: 10.1097/BOR.0b013e32835b1352 PubMedCrossRefGoogle Scholar
  23. 23.
    Hunter MP, Ismail N, Zhang X, Aguda BD, Lee EJ, Yu L, Xiao T, Schafer J, Lee ML, Schmittgen TD, Nana-Sinkam SP, Jarjoura D, Marsh CB (2008) Detection of microRNA expression in human peripheral blood microvesicles. PLoS ONE 3(11):e3694. doi: 10.1371/journal.pone.0003694 PubMedCrossRefGoogle Scholar
  24. 24.
    Igoucheva O, Alexeev V (2009) MicroRNA-dependent regulation of cKit in cutaneous melanoma. Biochem Biophys Res Commun 379(3):790–794. doi: 10.1016/j.bbrc.2008.12.152 PubMedCrossRefGoogle Scholar
  25. 25.
    Ishida M, Selaru FM (2013) miRNA-based therapeutic strategies. Curr Anesthesiol Rep 1(1):63–70. doi: 10.1007/s40139-012-0004-5 PubMedGoogle Scholar
  26. 26.
    Jiang X, Tsitsiou E, Herrick SE, Lindsay MA (2010) MicroRNAs and the regulation of fibrosis. FEBS J 277(9):2015–2021. doi: 10.1111/j.1742-4658.2010.07632.x PubMedCrossRefGoogle Scholar
  27. 27.
    Kajihara I, Jinnin M, Yamane K, Makino T, Honda N, Igata T, Masuguchi S, Fukushima S, Okamoto Y, Hasegawa M, Fujimoto M, Ihn H (2012) Increased accumulation of extracellular thrombospondin-2 due to low degradation activity stimulates type I collagen expression in scleroderma fibroblasts. Am J Pathol 180(2):703–714. doi: 10.1016/j.ajpath.2011.10.030 PubMedCrossRefGoogle Scholar
  28. 28.
    Karakikes I, Chaanine AH, Kang S, Mukete BN, Jeong D, Zhang S, Hajjar RJ, Lebeche D (2013) Therapeutic cardiac-targeted delivery of miR-1 reverses pressure overload-induced cardiac hypertrophy and attenuates pathological remodeling. J Am Heart Assoc 2(2):e000078. doi: 10.1161/JAHA.113.000078 PubMedCrossRefGoogle Scholar
  29. 29.
    Kashiyama K, Mitsutake N, Matsuse M, Ogi T, Saenko VA, Ujifuku K, Utani A, Hirano A, Yamashita S (2012) miR-196a downregulation increases the expression of type I and III collagens in keloid fibroblasts. J Invest Dermatol 132(6):1597–1604. doi: 10.1038/jid.2012.22 PubMedCrossRefGoogle Scholar
  30. 30.
    Kawashita Y, Jinnin M, Makino T, Kajihara I, Makino K, Honda N, Masuguchi S, Fukushima S, Inoue Y, Ihn H (2011) Circulating miR-29a levels in patients with scleroderma spectrum disorder. J Dermatol Sci 61(1):67–69. doi: 10.1016/j.jdermsci.2010.11.007 PubMedCrossRefGoogle Scholar
  31. 31.
    Kumarswamy R, Volkmann I, Thum T (2011) Regulation and function of miRNA-21 in health and disease. RNA Biol 8(5):706–713. doi: 10.4161/rna.8.5.16154 PubMedCrossRefGoogle Scholar
  32. 32.
    Lamouille S, Subramanyam D, Blelloch R, Derynck R (2013) Regulation of epithelial–mesenchymal and mesenchymal–epithelial transitions by microRNAs. Curr Opin Cell Biol 25(2):200–207. doi: 10.1016/ PubMedCrossRefGoogle Scholar
  33. 33.
    Lanford RE, Hildebrandt-Eriksen ES, Petri A, Persson R, Lindow M, Munk ME, Kauppinen S, Orum H (2010) Therapeutic silencing of microRNA-122 in primates with chronic hepatitis C virus infection. Science 327(5962):198–201. doi: 10.1126/science.1178178 PubMedCrossRefGoogle Scholar
  34. 34.
    Li H, Yang R, Fan X, Gu T, Zhao Z, Chang D, Wang W (2012) MicroRNA array analysis of microRNAs related to systemic scleroderma. Rheumatol Int 32(2):307–313. doi: 10.1007/s00296-010-1615-y PubMedCrossRefGoogle Scholar
  35. 35.
    Lindow M, Kauppinen S (2012) Discovering the first microRNA-targeted drug. J Cell Biol 199(3):407–412. doi: 10.1083/jcb.201208082 PubMedCrossRefGoogle Scholar
  36. 36.
    Liu Y, Yang D, Xiao Z, Zhang M (2012) miRNA expression profiles in keloid tissue and corresponding normal skin tissue. Aesthet Plast Surg 36(1):193–201. doi: 10.1007/s00266-011-9773-1 CrossRefGoogle Scholar
  37. 37.
    Liu Z, Lu CL, Cui LP, Hu YL, Yu Q, Jiang Y, Ma T, Jiao DK, Wang D, Jia CY (2012) MicroRNA-146a modulates TGF-beta1-induced phenotypic differentiation in human dermal fibroblasts by targeting SMAD4. Arch Dermatol Res 304(3):195–202. doi: 10.1007/s00403-011-1178-0 PubMedCrossRefGoogle Scholar
  38. 38.
    Makino K, Jinnin M, Hirano A, Yamane K, Eto M, Kusano T, Honda N, Kajihara I, Makino T, Sakai K, Masuguchi S, Fukushima S, Ihn H (2013) The downregulation of microRNA let-7a contributes to the excessive expression of type I collagen in systemic and localized scleroderma. J Immunol 190(8):3905–3915. doi: 10.4049/jimmunol.1200822 PubMedCrossRefGoogle Scholar
  39. 39.
    Makino K, Jinnin M, Kajihara I, Honda N, Sakai K, Masuguchi S, Fukushima S, Inoue Y, Ihn H (2012) Circulating miR-142-3p levels in patients with systemic sclerosis. Clin Exp Dermatol 37(1):34–39. doi: 10.1111/j.1365-2230.2011.04158.x PubMedCrossRefGoogle Scholar
  40. 40.
    Mattes J, Collison A, Plank M, Phipps S, Foster PS (2009) Antagonism of microRNA-126 suppresses the effector function of TH2 cells and the development of allergic airways disease. Proc Natl Acad Sci USA 106(44):18704–18709. doi: 10.1073/pnas.0905063106 PubMedCrossRefGoogle Scholar
  41. 41.
    Maurer B, Stanczyk J, Jungel A, Akhmetshina A, Trenkmann M, Brock M, Kowal-Bielecka O, Gay RE, Michel BA, Distler JH, Gay S, Distler O (2010) MicroRNA-29, a key regulator of collagen expression in systemic sclerosis. Arthr Rheum 62(6):1733–1743. doi: 10.1002/art.27443 CrossRefGoogle Scholar
  42. 42.
    Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL, Peterson A, Noteboom J, O’Briant KC, Allen A, Lin DW, Urban N, Drescher CW, Knudsen BS, Stirewalt DL, Gentleman R, Vessella RL, Nelson PS, Martin DB, Tewari M (2008) Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci USA 105(30):10513–10518. doi: 10.1073/pnas.0804549105 PubMedCrossRefGoogle Scholar
  43. 43.
    Molnar V, Tamasi V, Bakos B, Wiener Z, Falus A (2008) Changes in miRNA expression in solid tumors: an miRNA profiling in melanomas. Semin Cancer Biol 18(2):111–122. doi: 10.1016/j.semcancer.2008.01.001 PubMedCrossRefGoogle Scholar
  44. 44.
    Ning MS, Andl T (2013) Control by a hair’s breadth: the role of microRNAs in the skin. Cell Mol Life Sci 70(7):1149–1169. doi: 10.1007/s00018-012-1117-z PubMedCrossRefGoogle Scholar
  45. 45.
    Palmer TD, Rosman GJ, Osborne WR, Miller AD (1991) Genetically modified skin fibroblasts persist long after transplantation but gradually inactivate introduced genes. Proc Natl Acad Sci USA 88(4):1330–1334PubMedCrossRefGoogle Scholar
  46. 46.
    Parapuram SK, Shi-wen X, Elliott C, Welch ID, Jones H, Baron M, Denton CP, Abraham DJ, Leask A (2011) Loss of PTEN expression by dermal fibroblasts causes skin fibrosis. J Invest Dermatol 131(10):1996–2003. doi: 10.1038/jid.2011.156 PubMedCrossRefGoogle Scholar
  47. 47.
    Pastar I, Khan AA, Stojadinovic O, Lebrun EA, Medina MC, Brem H, Kirsner RS, Jimenez JJ, Leslie C, Tomic-Canic M (2012) Induction of specific microRNAs inhibits cutaneous wound healing. J Biol Chem 287(35):29324–29335. doi: 10.1074/jbc.M112.382135 PubMedCrossRefGoogle Scholar
  48. 48.
    Patel V, Noureddine L (2012) MicroRNAs and fibrosis. Curr Opin Nephrol Hypertens 21(4):410–416. doi: 10.1097/MNH.0b013e328354e559 PubMedCrossRefGoogle Scholar
  49. 49.
    Peng WJ, Tao JH, Mei B, Chen B, Li BZ, Yang GJ, Zhang Q, Yao H, Wang BX, He Q, Wang J (2012) MicroRNA-29: a potential therapeutic target for systemic sclerosis. Expert Opin Ther Targets 16(9):875–879. doi: 10.1517/14728222.2012.708339 PubMedCrossRefGoogle Scholar
  50. 50.
    Postlethwaite AE, Shigemitsu H, Kanangat S (2004) Cellular origins of fibroblasts: possible implications for organ fibrosis in systemic sclerosis. Curr Opin Rheumatol 16(6):733–738PubMedCrossRefGoogle Scholar
  51. 51.
    Qu L, Liu A, Zhou L, He C, Grossman PH, Moy RL, Mi QS, Ozog D (2012) Clinical and molecular effects on mature burn scars after treatment with a fractional CO(2) laser. Lasers Surg Med 44(7):517–524. doi: 10.1002/lsm.22055 PubMedCrossRefGoogle Scholar
  52. 52.
    Romano C, Schepis C (2012) PTEN gene: a model for genetic diseases in dermatology. Sci World J 2012:252457. doi: 10.1100/2012/252457 CrossRefGoogle Scholar
  53. 53.
    Sand M, Gambichler T, Sand D, Skrygan M, Altmeyer P, Bechara FG (2009) MicroRNAs and the skin: tiny players in the body’s largest organ. J Dermatol Sci 53(3):169–175. doi: 10.1016/j.jdermsci.2008.10.004 PubMedCrossRefGoogle Scholar
  54. 54.
    Satoh M, Chan JY, Ceribelli A, Vazquez del-Mercado M, Chan EK (2013) Autoantibodies to Argonaute 2 (Su antigen). Adv Exp Med Biol 768:45–59. doi: 10.1007/978-1-4614-5107-5_4 PubMedCrossRefGoogle Scholar
  55. 55.
    Sayed D, Rane S, Lypowy J, He M, Chen IY, Vashistha H, Yan L, Malhotra A, Vatner D, Abdellatif M (2008) MicroRNA-21 targets Sprouty2 and promotes cellular outgrowths. Mol Biol Cell 19(8):3272–3282. doi: 10.1091/mbc.E08-02-0159 PubMedCrossRefGoogle Scholar
  56. 56.
    Schlauder SM, Ahmad A, Horn TD (2009) Dicer and micro-RNAs in cutaneous disease. J Cutan Pathol 36(5):607–610. doi: 10.1111/j.1600-0560.2009.01311.x PubMedCrossRefGoogle Scholar
  57. 57.
    Schneider MR (2012) MicroRNAs as novel players in skin development, homeostasis and disease. Br J Dermatol 166(1):22–28. doi: 10.1111/j.1365-2133.2011.10568.x PubMedCrossRefGoogle Scholar
  58. 58.
    Sing T, Jinnin M, Yamane K, Honda N, Makino K, Kajihara I, Makino T, Sakai K, Masuguchi S, Fukushima S, Ihn H (2012) microRNA-92a expression in the sera and dermal fibroblasts increases in patients with scleroderma. Rheumatology 51(9):1550–1556. doi: 10.1093/rheumatology/kes120 PubMedCrossRefGoogle Scholar
  59. 59.
    Siprashvili Z, Khavari PA (2004) Lentivectors for regulated and reversible cutaneous gene delivery. Mol Ther J Am Soc Gene Ther 9(1):93–100CrossRefGoogle Scholar
  60. 60.
    Sonkoly E, Stahle M, Pivarcsi A (2008) MicroRNAs: novel regulators in skin inflammation. Clin Exp Dermatol 33(3):312–315. doi: 10.1111/j.1365-2230.2008.02804.x PubMedCrossRefGoogle Scholar
  61. 61.
    Sonkoly E, Wei T, Janson PC, Saaf A, Lundeberg L, Tengvall-Linder M, Norstedt G, Alenius H, Homey B, Scheynius A, Stahle M, Pivarcsi A (2007) MicroRNAs: novel regulators involved in the pathogenesis of psoriasis? PLoS ONE 2(7):e610. doi: 10.1371/journal.pone.0000610 PubMedCrossRefGoogle Scholar
  62. 62.
    Tan WQ, Gao ZJ, Xu JH, Yao HP (2011) Inhibiting scar formation in vitro and in vivo by adenovirus-mediated mutant Smad4: a preliminary report. Exp Dermatol 20(2):119–124. doi: 10.1111/j.1600-0625.2010.01186.x PubMedCrossRefGoogle Scholar
  63. 63.
    Tang O, Chen XM, Shen S, Hahn M, Pollock CA (2013) miRNA-200b represses transforming growth factor-beta1-induced EMT and fibronectin expression in kidney proximal tubular cells. Am J Physiol Renal Physiol 304(10):F1266–F1273. doi: 10.1152/ajprenal.00302.2012 PubMedCrossRefGoogle Scholar
  64. 64.
    Thombs BD, Haines JM, Bresnick MG, Magyar-Russell G, Fauerbach JA, Spence RJ (2007) Depression in burn reconstruction patients: symptom prevalence and association with body image dissatisfaction and physical function. Gen Hosp Psychiatry 29(1):14–20. doi: 10.1016/j.genhosppsych.2006.09.002 PubMedCrossRefGoogle Scholar
  65. 65.
    Thombs BD, Notes LD, Lawrence JW, Magyar-Russell G, Bresnick MG, Fauerbach JA (2008) From survival to socialization: a longitudinal study of body image in survivors of severe burn injury. J Psychosom Res 64(2):205–212. doi: 10.1016/j.jpsychores.2007.09.003 PubMedCrossRefGoogle Scholar
  66. 66.
    Thum T, Gross C, Fiedler J, Fischer T, Kissler S, Bussen M, Galuppo P, Just S, Rottbauer W, Frantz S, Castoldi M, Soutschek J, Koteliansky V, Rosenwald A, Basson MA, Licht JD, Pena JT, Rouhanifard SH, Muckenthaler MU, Tuschl T, Martin GR, Bauersachs J, Engelhardt S (2008) MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts. Nature 456(7224):980–984. doi: 10.1038/nature07511 PubMedCrossRefGoogle Scholar
  67. 67.
    Tili E, Michaille JJ, Gandhi V, Plunkett W, Sampath D, Calin GA (2007) miRNAs and their potential for use against cancer and other diseases. Future Oncol 3(5):521–537. doi: 10.2217/14796694.3.5.521 PubMedCrossRefGoogle Scholar
  68. 68.
    Valastyan S, Reinhardt F, Benaich N, Calogrias D, Szasz AM, Wang ZC, Brock JE, Richardson AL, Weinberg RA (2009) A pleiotropically acting microRNA, miR-31, inhibits breast cancer metastasis. Cell 137(6):1032–1046. doi: 10.1016/j.cell.2009.03.047 PubMedCrossRefGoogle Scholar
  69. 69.
    Valenti R, Huber V, Iero M, Filipazzi P, Parmiani G, Rivoltini L (2007) Tumor-released microvesicles as vehicles of immunosuppression. Cancer Res 67(7):2912–2915. doi: 10.1158/0008-5472.CAN-07-0520 PubMedCrossRefGoogle Scholar
  70. 70.
    Varga J (2011) Systemic sclerosis (scleroderma) and related disorders. In: Harrison’s principles of internal medicine, 18th edn. McGraw-Hill, New YorkGoogle Scholar
  71. 71.
    Vettori S, Gay S, Distler O (2012) Role of MicroRNAs in Fibrosis. Open Rheumatol J 6:130–139. doi: 10.2174/1874312901206010130 PubMedCrossRefGoogle Scholar
  72. 72.
    Wang T, Feng Y, Sun H, Zhang L, Hao L, Shi C, Wang J, Li R, Ran X, Su Y, Zou Z (2012) miR-21 regulates skin wound healing by targeting multiple aspects of the healing process. Am J Pathol 181(6):1911–1920. doi: 10.1016/j.ajpath.2012.08.022 PubMedCrossRefGoogle Scholar
  73. 73.
    Wang Y, Huang C, Reddy Chintagari N, Bhaskaran M, Weng T, Guo Y, Xiao X, Liu L (2013) miR-375 regulates rat alveolar epithelial cell trans-differentiation by inhibiting Wnt/beta-catenin pathway. Nucleic Acids Res 41(6):3833–3844. doi: 10.1093/nar/gks1460 PubMedCrossRefGoogle Scholar
  74. 74.
    Wei J, Bhattacharyya S, Tourtellotte WG, Varga J (2011) Fibrosis in systemic sclerosis: emerging concepts and implications for targeted therapy. Autoimmun Rev 10(5):267–275. doi: 10.1016/j.autrev.2010.09.015 PubMedCrossRefGoogle Scholar
  75. 75.
    Wynn TA, Ramalingam TR (2012) Mechanisms of fibrosis: therapeutic translation for fibrotic disease. Nat Med 18(7):1028–1040. doi: 10.1038/nm.2807 PubMedCrossRefGoogle Scholar
  76. 76.
    Xiao J, Yang B, Lin H, Lu Y, Luo X, Wang Z (2007) Novel approaches for gene-specific interference via manipulating actions of microRNAs: examination on the pacemaker channel genes HCN2 and HCN4. J Cell Physiol 212(2):285–292. doi: 10.1002/jcp.21062 PubMedCrossRefGoogle Scholar
  77. 77.
    Zhang L, Huang J, Yang N, Greshock J, Megraw MS, Giannakakis A, Liang S, Naylor TL, Barchetti A, Ward MR, Yao G, Medina A, O’Brien-Jenkins A, Katsaros D, Hatzigeorgiou A, Gimotty PA, Weber BL, Coukos G (2006) microRNAs exhibit high frequency genomic alterations in human cancer. Proc Natl Acad Sci USA 103(24):9136–9141. doi: 10.1073/pnas.0508889103 PubMedCrossRefGoogle Scholar
  78. 78.
    Zhu H, Li Y, Qu S, Luo H, Zhou Y, Wang Y, Zhao H, You Y, Xiao X, Zuo X (2012) MicroRNA expression abnormalities in limited cutaneous scleroderma and diffuse cutaneous scleroderma. J Clin Immunol 32(3):514–522. doi: 10.1007/s10875-011-9647-y PubMedCrossRefGoogle Scholar
  79. 79.
    Zhu H, Luo H, Li Y, Zhou Y, Jiang Y, Chai J, Xiao X, You Y, Zuo X (2013) MicroRNA-21 in scleroderma fibrosis and its function in TGF-beta-regulated fibrosis-related genes expression. J Clin Immunol 33(6):1100–1109. doi: 10.1007/s10875-013-9896-z PubMedCrossRefGoogle Scholar
  80. 80.
    Beyer C, Dees C, Distler JH (2013) Morphogen pathways as molecular targets for the treatment of fibrosis in systemic sclerosis. Arch Dermatol Res 305:1–8PubMedCrossRefGoogle Scholar

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

Personalised recommendations