Advertisement

Orchestrated Role of microRNAs in Skin Development and Regeneration

  • Natalia V. BotchkarevaEmail author
  • Rui Yi
Chapter
  • 382 Downloads
Part of the Stem Cell Biology and Regenerative Medicine book series (STEMCELL)

Abstract

MicroRNA (miRNA)-dependent control of gene expression is one of the important components of epigenetics that plays a fundamental role in the balancing and fine-tuning of lineage-specific differentiation programs in many organs including skin. Skin development is governed by bi-directional interactions between the epithelium and mesenchyme. During skin embryogenesis, multi-potent progenitors within the single-layered surface epithelium differentiate to form the multi-layered epidermis and its appendages, including the hair follicle. Skin and hair follicle development is tightly regulated by a balance of gene activation and silencing. miRNAs play indispensable roles in the formation of functional skin and its appendages, by orchestrating gene expression programs in a spatiotemporally specific manner, and also play important roles in a variety of skin diseases miRNAs. Study of the non-coding genome not only advances our understanding of the fundamental biological roles of miRNAs in healthy organisms, but will further allow for the development of novel therapeutic modalities involving targeting non-coding RNAs for many diseases including skin pathologies.

References

  1. 1.
    Ha M, Kim VN. Regulation of microRNA biogenesis. Nat Rev Mol Cell Biol. 2014;15(8):509–24.PubMedCrossRefGoogle Scholar
  2. 2.
    Chang TC, Pertea M, Lee S, Salzberg SL, Mendell JT. Genome-wide annotation of microRNA primary transcript structures reveals novel regulatory mechanisms. Genome Res. 2015;25(9):1401–9.PubMedPubMedCentralCrossRefGoogle Scholar
  3. 3.
    Landgraf P, Rusu M, Sheridan R, Sewer A, Iovino N, Aravin A, et al. A mammalian microRNA expression atlas based on small RNA library sequencing. Cell. 2007;129(7):1401–14.PubMedPubMedCentralCrossRefGoogle Scholar
  4. 4.
    Wang D, Zhang Z, O’Loughlin E, Wang L, Fan X, Lai EC, et al. MicroRNA-205 controls neonatal expansion of skin stem cells by modulating the PI(3)K pathway. Nat Cell Biol. 2013;15(10):1153–63.PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    Adam RC, Yang H, Rockowitz S, Larsen SB, Nikolova M, Oristian DS, et al. Pioneer factors govern super-enhancer dynamics in stem cell plasticity and lineage choice. Nature. 2015;521(7552):366–70.PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Marson A, Levine SS, Cole MF, Frampton GM, Brambrink T, Johnstone S, et al. Connecting microRNA genes to the core transcriptional regulatory circuitry of embryonic stem cells. Cell. 2008;134(3):521–33.PubMedPubMedCentralCrossRefGoogle Scholar
  7. 7.
    Suzuki HI, Yamagata K, Sugimoto K, Iwamoto T, Kato S, Miyazono K. Modulation of microRNA processing by p53. Nature. 2009;460(7254):529–33.PubMedCrossRefGoogle Scholar
  8. 8.
    Davis BN, Hilyard AC, Lagna G, Hata A. SMAD proteins control DROSHA-mediated microRNA maturation. Nature. 2008;454(7200):56–61.PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Kawai S, Amano A. BRCA1 regulates microRNA biogenesis via the DROSHA microprocessor complex. J Cell Biol. 2012;197(2):201–8.PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Krell J, Stebbing J, Frampton AE, Carissimi C, Harding V, De Giorgio A, et al. The role of TP53 in miRNA loading onto AGO2 and in remodelling the miRNA-mRNA interaction network. Lancet. 2015;385 Suppl 1:S15.PubMedCrossRefGoogle Scholar
  11. 11.
    Mori M, Triboulet R, Mohseni M, Schlegelmilch K, Shrestha K, Camargo FD, et al. Hippo signaling regulates microprocessor and links cell-density-dependent miRNA biogenesis to cancer. Cell. 2014;156(5):893–906.PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    Alarcon CR, Lee H, Goodarzi H, Halberg N, Tavazoie SF. N6-methyladenosine marks primary microRNAs for processing. Nature. 2015;519(7544):482–5.PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    Lund E, Guttinger S, Calado A, Dahlberg JE, Kutay U. Nuclear export of microRNA precursors. Science. 2004;303(5654):95–8.PubMedCrossRefGoogle Scholar
  14. 14.
    Yi R, Qin Y, Macara IG, Cullen BR. Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs. Genes Dev. 2003;17(24):3011–6.PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Yi R, Doehle BP, Qin Y, Macara IG, Cullen BR. Overexpression of exportin 5 enhances RNA interference mediated by short hairpin RNAs and microRNAs. RNA. 2005;11(2):220–6.PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    Xie M, Li M, Vilborg A, Lee N, Shu MD, Yartseva V, et al. Mammalian 5′-capped microRNA precursors that generate a single microRNA. Cell. 2013;155(7):1568–80.PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Andl T, Murchison EP, Liu F, Zhang Y, Yunta-Gonzalez M, Tobias JW, et al. The miRNA-processing enzyme dicer is essential for the morphogenesis and maintenance of hair follicles. Current Biol CB. 2006;16(10):1041–9.CrossRefGoogle Scholar
  18. 18.
    Teta M, Choi YS, Okegbe T, Wong G, Tam OH, Chong MM, et al. Inducible deletion of epidermal Dicer and Drosha reveals multiple functions for miRNAs in postnatal skin. Development. 2012;139(8):1405–16.PubMedPubMedCentralCrossRefGoogle Scholar
  19. 19.
    Wang D, Zhang Z, O’Loughlin E, Lee T, Houel S, O’Carroll D, et al. Quantitative functions of Argonaute proteins in mammalian development. Genes Dev. 2012;26(7):693–704.PubMedPubMedCentralCrossRefGoogle Scholar
  20. 20.
    Yi R, O’Carroll D, Pasolli HA, Zhang Z, Dietrich FS, Tarakhovsky A, et al. Morphogenesis in skin is governed by discrete sets of differentially expressed microRNAs. Nat Genet. 2006;38(3):356–62.PubMedCrossRefGoogle Scholar
  21. 21.
    Yi R, Pasolli HA, Landthaler M, Hafner M, Ojo T, Sheridan R, et al. DGCR8-dependent microRNA biogenesis is essential for skin development. Proc Natl Acad Sci U S A. 2009;106(2):498–502.PubMedCrossRefGoogle Scholar
  22. 22.
    Czech B, Hannon GJ. Small RNA sorting: matchmaking for Argonautes. Nat Rev Genet. 2011;12(1):19–31.PubMedCrossRefGoogle Scholar
  23. 23.
    Jonas S, Izaurralde E. Towards a molecular understanding of microRNA-mediated gene silencing. Nat Rev Genet. 2015;16(7):421–33.PubMedCrossRefGoogle Scholar
  24. 24.
    Rybak-Wolf A, Jens M, Murakawa Y, Herzog M, Landthaler M, Rajewsky N. A variety of dicer substrates in human and C. elegans. Cell. 2014;159(5):1153–67.PubMedCrossRefGoogle Scholar
  25. 25.
    Smibert P, Yang JS, Azzam G, Liu JL, Lai EC. Homeostatic control of Argonaute stability by microRNA availability. Nat Struct Mol Biol. 2013;20(7):789–95.PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Calabrese JM, Seila AC, Yeo GW, Sharp PA. RNA sequence analysis defines Dicer’s role in mouse embryonic stem cells. Proc Natl Acad Sci U S A. 2007;104(46):18097–102.PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Yoon JH, Jo MH, White EJ, De S, Hafner M, Zucconi BE, et al. AUF1 promotes let-7b loading on Argonaute 2. Genes Dev. 2015;29(15):1599–604.PubMedPubMedCentralCrossRefGoogle Scholar
  28. 28.
    Golden RJ, Chen B, Li T, Braun J, Manjunath H, Chen X, et al. An Argonaute phosphorylation cycle promotes microRNA-mediated silencing. Nature. 2017;542(7640):197–202.Google Scholar
  29. 29.
    La Rocca G, Olejniczak SH, Gonzalez AJ, Briskin D, Vidigal JA, Spraggon L, et al. In vivo, Argonaute-bound microRNAs exist predominantly in a reservoir of low molecular weight complexes not associated with mRNA. Proc Natl Acad Sci U S A. 2015;112(3):767–72.PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    Rissland OS, Hong SJ, Bartel DP. MicroRNA destabilization enables dynamic regulation of the miR-16 family in response to cell-cycle changes. Mol Cell. 2011;43(6):993–1004.PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Burroughs AM, Ando Y, de Hoon MJ, Tomaru Y, Nishibu T, Ukekawa R, et al. A comprehensive survey of 3′ animal miRNA modification events and a possible role for 3′ adenylation in modulating miRNA targeting effectiveness. Genome Res. 2010;20(10):1398–410.PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Jones MR, Blahna MT, Kozlowski E, Matsuura KY, Ferrari JD, Morris SA, et al. Zcchc11 uridylates mature miRNAs to enhance neonatal IGF-1 expression, growth, and survival. PLoS Genet. 2012;8(11):e1003105.PubMedPubMedCentralCrossRefGoogle Scholar
  33. 33.
    Jones MR, Quinton LJ, Blahna MT, Neilson JR, Fu S, Ivanov AR, et al. Zcchc11-dependent uridylation of microRNA directs cytokine expression. Nat Cell Biol. 2009;11(9):1157–63.PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    White AC, Khuu JK, Dang CY, Hu J, Tran KV, Liu A, et al. Stem cell quiescence acts as a tumour suppressor in squamous tumours. Nat Cell Biol. 2014;16(1):99–107.PubMedCrossRefGoogle Scholar
  35. 35.
    Riemondy K, Wang XJ, Torchia EC, Roop DR, Yi R. MicroRNA-203 represses selection and expansion of oncogenic Hras transformed tumor initiating cells. eLife 2015;4:e07004.  https://doi.org/10.7554/eLife.07004
  36. 36.
    Levy C, Khaled M, Robinson KC, Veguilla RA, Chen PH, Yokoyama S, et al. Lineage-specific transcriptional regulation of DICER by MITF in melanocytes. Cell. 2010;141(6):994–1005.PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Ito M, Liu Y, Yang Z, Nguyen J, Liang F, Morris RJ, et al. Stem cells in the hair follicle bulge contribute to wound repair but not to homeostasis of the epidermis. Nat Med. 2005;11(12):1351–4.PubMedCrossRefGoogle Scholar
  38. 38.
    Beck B, Blanpain C. Mechanisms regulating epidermal stem cells. EMBO J. 2012;31(9):2067–75.PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Yi R, Poy MN, Stoffel M, Fuchs E. A skin microRNA promotes differentiation by repressing ‘stemness’. Nature. 2008;452(7184):225–9.PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Zhang L, Stokes N, Polak L, Fuchs E. Specific microRNAs are preferentially expressed by skin stem cells to balance self-renewal and early lineage commitment. Cell Stem Cell. 2011;8(3):294–308.PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Ahmed MI, Alam M, Emelianov VU, Poterlowicz K, Patel A, Sharov AA, et al. MicroRNA-214 controls skin and hair follicle development by modulating the activity of the Wnt pathway. J Cell Biol. 2014;207(4):549–67.PubMedPubMedCentralCrossRefGoogle Scholar
  42. 42.
    Mardaryev AN, Ahmed MI, Vlahov NV, Fessing MY, Gill JH, Sharov AA, et al. Micro-RNA-31 controls hair cycle-associated changes in gene expression programs of the skin and hair follicle. FASEB J Off Publ Fed Am Soc Exp Biol. 2010;24(10):3869–81.Google Scholar
  43. 43.
    Lena AM, Shalom-Feuerstein R, Rivetti di Val Cervo P, Aberdam D, Knight RA, Melino G, et al. miR-203 represses ‘stemness’ by repressing DeltaNp63. Cell Death Differ. 2008;15(7):1187–95.PubMedCrossRefGoogle Scholar
  44. 44.
    Peng H, Park JK, Katsnelson J, Kaplan N, Yang W, Getsios S, et al. microRNA-103/107 family regulates multiple epithelial stem cell characteristics. Stem Cells. 2015;33(5):1642–56.PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Eichhorn SW, Guo H, McGeary SE, Rodriguez-Mias RA, Shin C, Baek D, et al. mRNA destabilization is the dominant effect of mammalian microRNAs by the time substantial repression ensues. Mol Cell. 2014;56(1):104–15.PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Chi SW, Zang JB, Mele A, Darnell RB. Argonaute HITS-CLIP decodes microRNA-mRNA interaction maps. Nature. 2009;460(7254):479–86.PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Hafner M, Landthaler M, Burger L, Khorshid M, Hausser J, Berninger P, et al. Transcriptome-wide identification of RNA-binding protein and microRNA target sites by PAR-CLIP. Cell 2010;141(1):129–41.Google Scholar
  48. 48.
    Mills AA, Zheng B, Wang XJ, Vogel H, Roop DR, Bradley A. p63 is a p53 homologue required for limb and epidermal morphogenesis. Nature. 1999;398(6729):708–13.PubMedCrossRefGoogle Scholar
  49. 49.
    Truong AB, Kretz M, Ridky TW, Kimmel R, Khavari PA. p63 regulates proliferation and differentiation of developmentally mature keratinocytes. Genes Dev. 2006;20(22):3185–97.PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Yuan S, Li F, Meng Q, Zhao Y, Chen L, Zhang H, et al. Post-transcriptional regulation of keratinocyte progenitor cell expansion, differentiation and hair follicle regression by miR-22. PLoS Genet. 2015;11(5):e1005253.PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Jackson SJ, Zhang Z, Feng D, Flagg M, O’Loughlin E, Wang D, et al. Rapid and widespread suppression of self-renewal by microRNA-203 during epidermal differentiation. Development. 2013;140(9):1882–91.PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Chen HL, Chiang PC, Lo CH, Lo YH, Hsu DK, Chen HY, et al. Galectin-7 regulates keratinocyte proliferation and differentiation through JNK-miR-203-p63 signaling. J Invest Dermatol. 2016;136(1):182–91.PubMedPubMedCentralCrossRefGoogle Scholar
  53. 53.
    Chikh A, Matin RN, Senatore V, Hufbauer M, Lavery D, Raimondi C, et al. iASPP/p63 autoregulatory feedback loop is required for the homeostasis of stratified epithelia. EMBO J. 2011;30(20):4261–73.PubMedPubMedCentralCrossRefGoogle Scholar
  54. 54.
    Kim KH, Cho EG, Yu SJ, Kang H, Kim YJ, Kim SH, et al. DeltaNp63 intronic miR-944 is implicated in the DeltaNp63-mediated induction of epidermal differentiation. Nucleic Acids Res. 2015;43(15):7462–79.PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Antonini D, Russo MT, De Rosa L, Gorrese M, Del Vecchio L, Missero C. Transcriptional repression of miR-34 family contributes to p63-mediated cell cycle progression in epidermal cells. J Invest Dermatol. 2010;130(5):1249–57.PubMedCrossRefGoogle Scholar
  56. 56.
    Amelio I, Lena AM, Viticchie G, Shalom-Feuerstein R, Terrinoni A, Dinsdale D, et al. miR-24 triggers epidermal differentiation by controlling actin adhesion and cell migration. J Cell Biol. 2012;199(2):347–63.PubMedPubMedCentralCrossRefGoogle Scholar
  57. 57.
    Peng H, Kaplan N, Hamanaka RB, Katsnelson J, Blatt H. Yang W, et al. microRNA-31/factor-inhibiting hypoxia-inducible factor 1 nexus regulates keratinocyte differentiation. Proc Natl Acad Sci U S A. 2012;109(35):14030–4.PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Blanpain C, Fuchs E. Epidermal homeostasis: a balancing act of stem cells in the skin. Nature reviews Molecular cell biology. 2009;10(3):207–17.Google Scholar
  59. 59.
    Millar SE. Molecular mechanisms regulating hair follicle development. The Journal of investigative dermatology. 2002;118(2):216–25.Google Scholar
  60. 60.
    Schmidt-Ullrich R, Paus R. Molecular principles of hair follicle induction and morphogenesis. Bioessays. 2005;27(3):247–61.Google Scholar
  61. 61.
    Andl T, Reddy ST, Gaddapara T, Millar SE. WNT signals are required for the initiation of hair follicle development. Dev Cell. 2002;2(5):643–53.PubMedCrossRefGoogle Scholar
  62. 62.
    Choi YS, Zhang Y, Xu M, Yang Y, Ito M, Peng T, et al. Distinct functions for Wnt/beta-catenin in hair follicle stem cell proliferation and survival and interfollicular epidermal homeostasis. Cell Stem Cell. 2013;13(6):720–33.PubMedPubMedCentralCrossRefGoogle Scholar
  63. 63.
    Fu J, Hsu W. Epidermal Wnt controls hair follicle induction by orchestrating dynamic signaling crosstalk between the epidermis and dermis. J Invest Dermatol. 2013;133(4):890–8.PubMedCrossRefGoogle Scholar
  64. 64.
    Sick S, Reinker S, Timmer J, Schlake T. WNT and DKK determine hair follicle spacing through a reaction-diffusion mechanism. Science. 2006;314(5804):1447–50.PubMedCrossRefGoogle Scholar
  65. 65.
    Tsai SY, Sennett R, Rezza A, Clavel C, Grisanti L, Zemla R, et al. Wnt/beta-catenin signaling in dermal condensates is required for hair follicle formation. Dev Biol. 2014;385(2):179–88.PubMedCrossRefGoogle Scholar
  66. 66.
    Enshell-Seijffers D, Lindon C, Kashiwagi M, Morgan BA. Beta-catenin activity in the dermal papilla regulates morphogenesis and regeneration of hair. Dev Cell. 2010;18(4):633–42.PubMedPubMedCentralCrossRefGoogle Scholar
  67. 67.
    Huelsken J, Vogel R, Erdmann B, Cotsarelis G, Birchmeier W. beta-Catenin controls hair follicle morphogenesis and stem cell differentiation in the skin. Cell. 2001;105(4):533–45.PubMedCrossRefGoogle Scholar
  68. 68.
    Vidal VP, Chaboissier MC, Lutzkendorf S, Cotsarelis G, Mill P, Hui CC, et al. Sox9 is essential for outer root sheath differentiation and the formation of the hair stem cell compartment. Curr Biol CB. 2005;15(15):1340–51.PubMedCrossRefGoogle Scholar
  69. 69.
    Blache P, van de Wetering M, Duluc I, Domon C, Berta P, Freund JN, et al. SOX9 is an intestine crypt transcription factor, is regulated by the Wnt pathway, and represses the CDX2 and MUC2 genes. J Cell Biol. 2004;166(1):37–47.PubMedPubMedCentralCrossRefGoogle Scholar
  70. 70.
    Liu JA, Wu MH, Yan CH, Chau BK, So H, Ng A, et al. Phosphorylation of Sox9 is required for neural crest delamination and is regulated downstream of BMP and canonical Wnt signaling. Proc Natl Acad Sci U S A. 2013;110(8):2882–7.PubMedPubMedCentralCrossRefGoogle Scholar
  71. 71.
    Mitra AK, Zillhardt M, Hua Y, Tiwari P, Murmann AE, Peter ME, et al. MicroRNAs reprogram normal fibroblasts into cancer-associated fibroblasts in ovarian cancer. Cancer Discov. 2012;2(12):1100–8.PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Penna E, Orso F, Cimino D, Tenaglia E, Lembo A, Quaglino E, et al. microRNA-214 contributes to melanoma tumour progression through suppression of TFAP2C. EMBO J. 2011;30(10):1990–2007.PubMedPubMedCentralCrossRefGoogle Scholar
  73. 73.
    Penna E, Orso F, Taverna D. miR-214 as a key hub that controls cancer networks: small player, multiple functions. J Invest Dermatol. 2015;135(4):960–9.PubMedCrossRefGoogle Scholar
  74. 74.
    Amelio I, Lena AM, Bonanno E, Melino G, Candi E. miR-24 affects hair follicle morphogenesis targeting Tcf-3. Cell Death Dis. 2013;4:e922.PubMedPubMedCentralCrossRefGoogle Scholar
  75. 75.
    DasGupta R, Fuchs E. Multiple roles for activated LEF/TCF transcription complexes during hair follicle development and differentiation. Development. 1999;126(20):4557–68.PubMedGoogle Scholar
  76. 76.
    Merrill BJ, Gat U, DasGupta R, Fuchs E. Tcf3 and Lef1 regulate lineage differentiation of multipotent stem cells in skin. Genes Dev. 2001;15(13):1688–705.PubMedPubMedCentralCrossRefGoogle Scholar
  77. 77.
    Botchkarev VA, Kishimoto J. Molecular control of epithelial-mesenchymal interactions during hair follicle cycling. J Invest Dermatol Symp Proc Soc Invest Dermatol Inc [and] Eur Soc Dermatol Res. 2003;8(1):46–55.CrossRefGoogle Scholar
  78. 78.
    Botchkareva NV, Ahluwalia G, Shander D. Apoptosis in the hair follicle. J Invest Dermatol. 2006;126(2):258–64.PubMedCrossRefGoogle Scholar
  79. 79.
    Lee J, Tumbar T. Hairy tale of signaling in hair follicle development and cycling. Semin Cell Dev Biol. 2012;23(8):906–16.PubMedPubMedCentralCrossRefGoogle Scholar
  80. 80.
    Luan L, Shi J, Yu Z, Andl T. The major miR-31 target genes STK40 and LATS2 and their implications in the regulation of keratinocyte growth and hair differentiation. Exp Dermatol. 2017;26(6):497–504.PubMedCrossRefGoogle Scholar
  81. 81.
    Botchkareva NV, Botchkarev VA, Gilchrest BA. Fate of melanocytes during development of the hair follicle pigmentary unit. J Invest Dermatol Symp Proc Soc Invest Dermatol Inc [and] Eur Soc Dermatol Res. 2003;8(1):76–9.CrossRefGoogle Scholar
  82. 82.
    Botchkareva NV, Khlgatian M, Longley BJ, Botchkarev VA, Gilchrest BA. SCF/c-kit signaling is required for cyclic regeneration of the hair pigmentation unit. FASEB J Off Publ Fed Am Soc Exp Biol. 2001;15(3):645–58.Google Scholar
  83. 83.
    Hemesath TJ, Steingrimsson E, McGill G, Hansen MJ, Vaught J, Hodgkinson CA, et al. Microphthalmia, a critical factor in melanocyte development, defines a discrete transcription factor family. Genes Dev. 1994;8(22):2770–80.PubMedCrossRefGoogle Scholar
  84. 84.
    Levy C, Khaled M, Fisher DE. MITF: master regulator of melanocyte development and melanoma oncogene. Trends Mol Med. 2006;12(9):406–14.PubMedCrossRefGoogle Scholar
  85. 85.
    Yavuzer U, Keenan E, Lowings P, Vachtenheim J, Currie G, Goding CR. The Microphthalmia gene product interacts with the retinoblastoma protein in vitro and is a target for deregulation of melanocyte-specific transcription. Oncogene. 1995;10(1):123–34.PubMedGoogle Scholar
  86. 86.
    Dong C, Wang H, Xue L, Dong Y, Yang L, Fan R, et al. Coat color determination by miR-137 mediated down-regulation of microphthalmia-associated transcription factor in a mouse model. RNA. 2012;18(9):1679–86.PubMedPubMedCentralCrossRefGoogle Scholar
  87. 87.
    Barrientos S, Stojadinovic O, Golinko MS, Brem H, Tomic-Canic M. Growth factors and cytokines in wound healing. Wound Repair Reg Off Publ Wound Healing Soc [and] European Tissue Repair Soc. 2008;16(5):585–601.Google Scholar
  88. 88.
    Li J, Chen J, Kirsner R. Pathophysiology of acute wound healing. Clin Dermatol. 2007;25(1):9–18.PubMedCrossRefGoogle Scholar
  89. 89.
    Schafer M, Werner S. Transcriptional control of wound repair. Annu Rev Cell Dev Biol. 2007;23:69–92.PubMedCrossRefGoogle Scholar
  90. 90.
    Shaw TJ, Martin P. Wound repair at a glance. J Cell Sci. 2009;122(Pt 18):3209–13.PubMedPubMedCentralCrossRefGoogle Scholar
  91. 91.
    Taylor G, Lehrer MS, Jensen PJ, Sun TT, Lavker RM. Involvement of follicular stem cells in forming not only the follicle but also the epidermis. Cell. 2000;102(4):451–61.PubMedCrossRefGoogle Scholar
  92. 92.
    Cotsarelis G. Epithelial stem cells: a folliculocentric view. J Invest Dermatol. 2006;126(7):1459–68.PubMedCrossRefGoogle Scholar
  93. 93.
    Langton AK, Herrick SE, Headon DJ. An extended epidermal response heals cutaneous wounds in the absence of a hair follicle stem cell contribution. J Invest Dermatol. 2008;128(5):1311–8.PubMedCrossRefGoogle Scholar
  94. 94.
    Levy V, Lindon C, Zheng Y, Harfe BD, Morgan BA. Epidermal stem cells arise from the hair follicle after wounding. FASEB J Off Publ Fed Am Soc Exp Biol. 2007;21(7):1358–66.Google Scholar
  95. 95.
    Abe R, Donnelly SC, Peng T, Bucala R, Metz CN. Peripheral blood fibrocytes: differentiation pathway and migration to wound sites. J Immunol. 2001;166(12):7556–62.PubMedCrossRefGoogle Scholar
  96. 96.
    Fathke C, Wilson L, Hutter J, Kapoor V, Smith A, Hocking A, et al. Contribution of bone marrow-derived cells to skin: collagen deposition and wound repair. Stem Cells. 2004;22(5):812–22.PubMedPubMedCentralCrossRefGoogle Scholar
  97. 97.
    Hinz B. Formation and function of the myofibroblast during tissue repair. J Invest Dermatol. 2007;127(3):526–37.PubMedCrossRefGoogle Scholar
  98. 98.
    Wu Y, Zhao RC, Tredget EE. Concise review: bone marrow-derived stem/progenitor cells in cutaneous repair and regeneration. Stem Cells. 2010;28(5):905–15.PubMedPubMedCentralGoogle Scholar
  99. 99.
    Bitterman PB, Rennard SI, Adelberg S, Crystal RG. Role of fibronectin as a growth factor for fibroblasts. J Cell Biol. 1983;97(6):1925–32.PubMedCrossRefGoogle Scholar
  100. 100.
    Eckes B, Colucci-Guyon E, Smola H, Nodder S, Babinet C, Krieg T, et al. Impaired wound healing in embryonic and adult mice lacking vimentin. J Cell Sci. 2000;113(Pt 13):2455–62.PubMedGoogle Scholar
  101. 101.
    Min LJ, Cui TX, Yahata Y, Yamasaki K, Shiuchi T, Liu HW, et al. Regulation of collagen synthesis in mouse skin fibroblasts by distinct angiotensin II receptor subtypes. Endocrinology. 2004;145(1):253–60.PubMedCrossRefGoogle Scholar
  102. 102.
    Tiedemann K, Malmstrom A, Westergren-Thorsson G. Cytokine regulation of proteoglycan production in fibroblasts: separate and synergistic effects. Matrix Biol J Int Soc Matrix Biol. 1997;15(7):469–78.CrossRefGoogle Scholar
  103. 103.
    Jaul E. Non-healing wounds: the geriatric approach. Arch Gerontol Geriatr. 2009;49(2):224–6.PubMedCrossRefGoogle Scholar
  104. 104.
    Sgonc R, Gruber J. Age-related aspects of cutaneous wound healing: a mini-review. Gerontology. 2013;59(2):159–64.PubMedCrossRefGoogle Scholar
  105. 105.
    Bentov I, Damodarasamy M, Plymate S, Reed MJ. Decreased proliferative capacity of aged dermal fibroblasts in a three dimensional matrix is associated with reduced IGF1R expression and activation. Biogerontology. 2014;15(4):329–37.PubMedPubMedCentralCrossRefGoogle Scholar
  106. 106.
    Gosain A, DiPietro LA. Aging and wound healing. World J Surg. 2004;28(3):321–6.PubMedCrossRefGoogle Scholar
  107. 107.
    Ghatak S, Chan YC, Khanna S, Banerjee J, Weist J, Roy S, et al. Barrier function of the repaired skin is disrupted following arrest of dicer in keratinocytes. Mol Ther. 2015;23(7):1201–10.PubMedPubMedCentralCrossRefGoogle Scholar
  108. 108.
    Devgan V, Nguyen BC, Oh H, Dotto GP. p21WAF1/Cip1 suppresses keratinocyte differentiation independently of the cell cycle through transcriptional up-regulation of the IGF-I gene. J Biol Chem. 2006;281(41):30463–70.PubMedCrossRefGoogle Scholar
  109. 109.
    Li D, Li X, Wang A, Meisgen F, Pivarcsi A, Sonkoly E, et al. MicroRNA-31 promotes skin wound healing by enhancing keratinocyte proliferation and migration. J Invest Dermatol. 2015;135(6):1676–85.PubMedCrossRefGoogle Scholar
  110. 110.
    Li D, Wang A, Liu X, Meisgen F, Grunler J, Botusan IR, et al. MicroRNA-132 enhances transition from inflammation to proliferation during wound healing. J Clin Invest. 2015;125(8):3008–26.PubMedPubMedCentralCrossRefGoogle Scholar
  111. 111.
    Joyce CE, Zhou X, Xia J, Ryan C, Thrash B, Menter A, et al. Deep sequencing of small RNAs from human skin reveals major alterations in the psoriasis miRNAome. Hum Mol Genet. 2011;20(20):4025–40.PubMedPubMedCentralCrossRefGoogle Scholar
  112. 112.
    Wang A, Landen NX, Meisgen F, Lohcharoenkal W, Stahle M, Sonkoly E, et al. MicroRNA-31 is overexpressed in cutaneous squamous cell carcinoma and regulates cell motility and colony formation ability of tumor cells. PLoS One. 2014;9(7):e103206.PubMedPubMedCentralCrossRefGoogle Scholar
  113. 113.
    Yan S, Xu Z, Lou F, Zhang L, Ke F, Bai J, et al. NF-kappaB-induced microRNA-31 promotes epidermal hyperplasia by repressing protein phosphatase 6 in psoriasis. Nat Commun. 2015;6:7652.PubMedPubMedCentralCrossRefGoogle Scholar
  114. 114.
    Durgan J, Tao G, Walters MS, Florey O, Schmidt A, Arbelaez V, et al. SOS1 and Ras regulate epithelial tight junction formation in the human airway through EMP1. EMBO Rep. 2015;16(1):87–96.PubMedCrossRefGoogle Scholar
  115. 115.
    Sun GG, Wang YD, Cui DW, Cheng YJ, Hu WN. Epithelial membrane protein 1 negatively regulates cell growth and metastasis in colorectal carcinoma. World J Gastroenterol. 2014;20(14):4001–10.PubMedPubMedCentralCrossRefGoogle Scholar
  116. 116.
    Sun GG, Wang YD, Lu YF, Hu WN. EMP1, a member of a new family of antiproliferative genes in breast carcinoma. Tumour Biol J Int Soc Oncodevelopmental Biol Med. 2014;35(4):3347–54.CrossRefGoogle Scholar
  117. 117.
    Li H, Chang L, Du WW, Gupta S, Khorshidi A, Sefton M, et al. Anti-microRNA-378a enhances wound healing process by upregulating integrin beta-3 and vimentin. Mol Ther. 2014;22(10):1839–50.PubMedPubMedCentralCrossRefGoogle Scholar
  118. 118.
    Gras C, Ratuszny D, Hadamitzky C, Zhang H, Blasczyk R, Figueiredo C. miR-145 contributes to hypertrophic scarring of the skin by inducing myofibroblast activity. Mol Med. 2015;21:296–304.PubMedPubMedCentralCrossRefGoogle Scholar
  119. 119.
    Kwan P, Ding J, Tredget EE. MicroRNA 181b regulates decorin production by dermal fibroblasts and may be a potential therapy for hypertrophic scar. PLoS One. 2015;10(4):e0123054.PubMedPubMedCentralCrossRefGoogle Scholar
  120. 120.
    Danielson KG, Baribault H, Holmes DF, Graham H, Kadler KE, Iozzo RV. Targeted disruption of decorin leads to abnormal collagen fibril morphology and skin fragility. J Cell Biol. 1997;136(3):729–43.PubMedPubMedCentralCrossRefGoogle Scholar
  121. 121.
    Jarvelainen H, Puolakkainen P, Pakkanen S, Brown EL, Hook M, Iozzo RV, et al. A role for decorin in cutaneous wound healing and angiogenesis. Wound Repair Reg Off Publ Wound Healing Soc [and] European Tissue Repair Soc. 2006;14(4):443–52.Google Scholar
  122. 122.
    Cheng J, Wang Y, Wang D, Wu Y. Identification of collagen 1 as a post-transcriptional target of miR-29b in skin fibroblasts: therapeutic implication for scar reduction. Am J Med Sci. 2013;346(2):98–103.PubMedCrossRefGoogle Scholar
  123. 123.
    Ciechomska M, O’Reilly S, Suwara M, Bogunia-Kubik K, van Laar JM. MiR-29a reduces TIMP-1 production by dermal fibroblasts via targeting TGF-beta activated kinase 1 binding protein 1, implications for systemic sclerosis. PLoS One. 2014;9(12):e115596.PubMedPubMedCentralCrossRefGoogle Scholar
  124. 124.
    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.PubMedCrossRefGoogle Scholar
  125. 125.
    Pastar I, Khan AA, Stojadinovic O, Lebrun EA, Medina MC, Brem H, et al. Induction of specific microRNAs inhibits cutaneous wound healing. J Biol Chem. 2012;287(35):29324–35.PubMedPubMedCentralCrossRefGoogle Scholar
  126. 126.
    Frank S, Stallmeyer B, Kampfer H, Kolb N, Pfeilschifter J. Leptin enhances wound re-epithelialization and constitutes a direct function of leptin in skin repair. J Clin Invest. 2000;106(4):501–9.PubMedPubMedCentralCrossRefGoogle Scholar
  127. 127.
    Murad A, Nath AK, Cha ST, Demir E, Flores-Riveros J, Sierra-Honigmann MR. Leptin is an autocrine/paracrine regulator of wound healing. FASEB J Off Publ Fed Am Soc Exp Biol. 2003;17(13):1895–7.Google Scholar
  128. 128.
    Tadokoro S, Ide S, Tokuyama R, Umeki H, Tatehara S, Kataoka S, et al. Leptin promotes wound healing in the skin. PLoS One. 2015;10(3):e0121242.PubMedPubMedCentralCrossRefGoogle Scholar
  129. 129.
    Ahmed MI, Mardaryev AN, Lewis CJ, Sharov AA, Botchkareva NV. MicroRNA-21 is an important downstream component of BMP signalling in epidermal keratinocytes. J Cell Sci. 2011;124(Pt 20):3399–404.PubMedPubMedCentralCrossRefGoogle Scholar
  130. 130.
    Lewis CJ, Mardaryev AN, Poterlowicz K, Sharova TY, Aziz A, Sharpe DT, et al. Bone morphogenetic protein signaling suppresses wound-induced skin repair by inhibiting keratinocyte proliferation and migration. J Invest Dermatol. 2014;134(3):827–37.PubMedCrossRefGoogle Scholar
  131. 131.
    Lewis CJ, Mardaryev AN, Sharpe DT, Botchkareva NV. Inhibition of bone morphogenetic protein signalling promotes wound healing in a human ex vivo model. Eur J Plast Surg. 2015;38(1):1–12.CrossRefGoogle Scholar
  132. 133.
    Madhyastha R, Madhyastha H, Nakajima Y, Omura S, Maruyama M. MicroRNA signature in diabetic wound healing: promotive role of miR-21 in fibroblast migration. Int Wound J. 2012;9(4):355–61.PubMedCrossRefGoogle Scholar
  133. 133.
    Geiger A, Walker A, Nissen E. Human fibrocyte-derived exosomes accelerate wound healing in genetically diabetic mice. Biochem Biophys Res Commun. 2015;467(2):303–9.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Centre for Skin SciencesUniversity of BradfordBradfordUK
  2. 2.Department of Molecular, Cellular and Developmental BiologyUniversity of Colorado, BoulderDenverUSA

Personalised recommendations