Abstract
MicroRNAs (miRNAs) are small noncoding RNA molecules ∼22 nucleotides in length that can post-transcriptionally repress gene expression. MiRNAs bind to their target messenger RNAs (mRNAs), leading to mRNA degradation or suppression of translation. miRNAs have recently been shown to play pivotal roles in skin development and are linked to various skin pathologies, cancer, and wound healing. Chronic wounds represent a major health burden and drain on resources and developing more effective treatments is therefore a necessity. Increase in the understanding of the regulation of chronic wound biology is therefore required to develop newer therapies. This review focuses on the role of miRNAs in cutaneous biology, the various methods of miRNA modulation, and the therapeutic opportunities in treatment of skin diseases and wound healing.
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References
Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116(2):281–297
Miranda KC, Huynh T, Tay Y, Ang YS, Tam WL, Thomson AM, Lim B, Rigoutsos I (2006) A pattern-based method for the identification of microRNA binding sites and their corresponding heteroduplexes. Cell 126(6):1203–1217
Banerjee J, Chan YC, Sen CK (2011) MicroRNAs in skin and wound healing. Physiol Genomics 43(10):543–556
Fuchs E (2008) Skin stem cells: rising to the surface. J Cell Biol 180(2):273–284
Blanpain C, Fuchs E (2009) Epidermal homeostasis: a balancing act of stem cells in the skin. Nat Rev Mol Cell Biol 10(3):207–217
Andl T, Murchison EP, Liu F, Zhang Y, Yunta-Gonzalez M, Tobias JW, Andl CD, Seykora JT, Hannon GJ, Millar SE (2006) The miRNA-processing enzyme dicer is essential for the morphogenesis and maintenance of hair follicles. Curr Biol 16(10):1041–1049
Yi R, O’Carroll D, Pasolli HA, Zhang Z, Dietrich FS, Tarakhovsky A, Fuchs E (2006) Morphogenesis in skin is governed by discrete sets of differentially expressed microRNAs. Nat Genet 38(3):356–362
Yi R, Pasolli HA, Landthaler M, Hafner M, Ojo T, Sheridan R, Sander C, O’Carroll D, Stoffel M, Tuschl T, Fuchs E (2009) Dgcr8-dependent microRNA biogenesis is essential for skin development. Proc Natl Acad Sci USA 106(2):498–502
Zhang L, Stokes N, Polak L, Fuchs E (2011) Specific microRNAs are preferentially expressed by skin stem cells to balance self-renewal and early lineage commitment. Cell Stem Cell 8(3):294–308
Yi R, Poy MN, Stoffel M, Fuchs E (2008) A skin microRNA promotes differentiation by repressing ‘stemness’. Nature 452(7184):225–229
Hildebrand J, Rutze M, Walz N, Gallinat S, Wenck H, Deppert W, Grundhoff A, Knott A (2011) A comprehensive analysis of microRNA expression during human keratinocyte differentiation in vitro and in vivo. J Invest Dermatol 131(1):20–29
Roy S, Sen CK (2011) MiRNA in innate immune responses: novel players in wound inflammation. Physiol Genomics 43(10):557–565
Sen CK (2009) Wound healing essentials: let there be oxygen. Wound Repair Regen 17(1):1–18
Zhu N, Zhang D, Chen S, Liu X, Lin L, Huang X, Guo Z, Liu J, Wang Y, Yuan W, Qin Y (2011) Endothelial enriched microRNAs regulate angiotensin ii-induced endothelial inflammation and migration. Atherosclerosis 215(2):286–293
Sen CK, Gordillo GM, Khanna S, Roy S (2009) Micromanaging vascular biology: tiny microRNAs play big band. J Vasc Res 46(6):527–540
Shilo S, Roy S, Khanna S, Sen CK (2008) Evidence for the involvement of miRNA in redox regulated angiogenic response of human microvascular endothelial cells. Arterioscler Thromb Vasc Biol 28(3):471–477
Chan YC, Khanna S, Roy S, Sen CK (2011) Mir-200b targets ets-1 and is down-regulated by hypoxia to induce angiogenic response of endothelial cells. J Biol Chem 286(3):2047–2056
Fish JE, Santoro MM, Morton SU, Yu S, Yeh RF, Wythe JD, Ivey KN, Bruneau BG, Stainier DY, Srivastava D (2008) Mir-126 regulates angiogenic signaling and vascular integrity. Dev Cell 15(2):272–284
Poliseno L, Salmena L, Zhang J, Carver B, Haveman WJ, Pandolfi PP (2010) A coding-independent function of gene and pseudogene mRNAs regulates tumour biology. Nature 465(7301):1033–1038
Dews M, Homayouni A, Yu D, Murphy D, Sevignani C, Wentzel E, Furth EE, Lee WM, Enders GH, Mendell JT, Thomas-Tikhonenko A (2006) Augmentation of tumor angiogenesis by a Myc-activated microRNA cluster. Nat Genet 38(9):1060–1065
Bonauer A, Carmona G, Iwasaki M, Mione M, Koyanagi M, Fischer A, Burchfield J, Fox H, Doebele C, Ohtani K, Chavakis E, Potente M, Tjwa M, Urbich C, Zeiher AM, Dimmeler S (2009) MicroRNA-92a controls angiogenesis and functional recovery of ischemic tissues in mice. Science 324(5935):1710–1713
Hua Z, Lv Q, Ye W, Wong CK, Cai G, Gu D, Ji Y, Zhao C, Wang J, Yang BB, Zhang Y (2006) MiRNA-directed regulation of vegf and other angiogenic factors under hypoxia. PLoS One 1:e116
Otsuka M, Zheng M, Hayashi M, Lee JD, Yoshino O, Lin S, Han J (2008) Impaired microRNA processing causes corpus luteum insufficiency and infertility in mice. J Clin Invest 118(5):1944–1954
Brauchle M, Angermeyer K, Hubner G, Werner S (1994) Large induction of keratinocyte growth factor expression by serum growth factors and pro-inflammatory cytokines in cultured fibroblasts. Oncogene 9(11):3199–3204
Takehara K (2000) Growth regulation of skin fibroblasts. J Dermatol Sci 24(suppl 1):S70–S77
Chan SY, Loscalzo J (2010) MicroRNA-210: a unique and pleiotropic hypoxamir. Cell Cycle 9(6):1072–1083
Guimbellot JS, Erickson SW, Mehta T, Wen H, Page GP, Sorscher EJ, Hong JS (2009) Correlation of microRNA levels during hypoxia with predicted target mRNAs through genome-wide microarray analysis. BMC Med Genomics 2:15
Chan SY, Zhang YY, Hemann C, Mahoney CE, Zweier JL, Loscalzo J (2009) MicroRNA-210 controls mitochondrial metabolism during hypoxia by repressing the iron-sulfur cluster assembly proteins iscu1/2. Cell Metab 10(4):273–284
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. Arthritis Rheum 62(6):1733–1743
Beanes SR, Hu FY, Soo C, Dang CM, Urata M, Ting K, Atkinson JB, Benhaim P, Hedrick MH, Lorenz HP (2002) Confocal microscopic analysis of scarless repair in the fetal rat: defining the transition. Plast Reconstr Surg 109(1):160–170
Beanes SR, Dang C, Soo C, Ting K (2003) Skin repair and scar formation: the central role of tgf-beta. Expert Rev Mol Med 5(8):1–22
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):203–209
Yan HL, Xue G, Mei Q, Wang YZ, Ding FX, Liu MF, Lu MH, Tang Y, Yu HY, Sun SH (2009) Repression of the mir-17-92 cluster by p53 has an important function in hypoxia-induced apoptosis. EMBO J 28(18):2719–2732
van Rooij E, Sutherland LB, Thatcher JE, DiMaio JM, Naseem RH, Marshall WS, Hill JA, Olson EN (2008) Dysregulation of microRNAs after myocardial infarction reveals a role of mir-29 in cardiac fibrosis. Proc Natl Acad Sci U S A 105(35):13027–13032
Kato M, Zhang J, Wang M, Lanting L, Yuan H, Rossi JJ, Natarajan R (2007) MicroRNA-192 in diabetic kidney glomeruli and its function in tgf-beta-induced collagen expression via inhibition of e-box repressors. Proc Natl Acad Sci USA 104(9):3432–3437
Tinkle CL, Lechler T, Pasolli HA, Fuchs E (2004) Conditional targeting of e-cadherin in skin: insights into hyperproliferative and degenerative responses. Proc Natl Acad Sci USA 101(2):552–557
Tunggal JA, Helfrich I, Schmitz A, Schwarz H, Gunzel D, Fromm M, Kemler R, Krieg T, Niessen CM (2005) E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions. EMBO J 24(6):1146–1156
Park SM, Gaur AB, Lengyel E, Peter ME (2008) The mir-200 family determines the epithelial phenotype of cancer cells by targeting the e-cadherin repressors zeb1 and zeb2. Genes Dev 22(7):894–907
Korpal M, Lee ES, Hu G, Kang Y (2008) The mir-200 family inhibits epithelial-mesenchymal transition and cancer cell migration by direct targeting of e-cadherin transcriptional repressors zeb1 and zeb2. J Biol Chem 283(22):14910–14914
Gregory PA, Bert AG, Paterson EL, Barry SC, Tsykin A, Farshid G, Vadas MA, Khew-Goodall Y, Goodall GJ (2008) The mir-200 family and mir-205 regulate epithelial to mesenchymal transition by targeting zeb1 and sip1. Nat Cell Biol 10(5):593–601
Kosmadaki MG, Naif A, Hee-Young P (2010) Recent progresses in understanding pigmentation. G Ital Dermatol Venereol 145(1):47–55
Neer RM (1975) The evolutionary significance of vitamin d, skin pigment, and ultraviolet light. Am J Phys Anthropol 43(3):409–416
Zhu Z, He J, Jia X, Jiang J, Bai R, Yu X, Lv L, Fan R, He X, Geng J, You R, Dong Y, Qiao D, Lee KB, Smith GW, Dong C (2010) MicroRNA-25 functions in regulation of pigmentation by targeting the transcription factor MITF in alpaca (lama pacos) skin melanocytes. Domest Anim Endocrinol 38(3):200–209
Wu D, Chen JS, Chang DC, Lin SL (2008) Mir-434-5p mediates skin whitening and lightening. Clin Cosmet Investig Dermatol 1:19–35
Biswas S, Roy S, Banerjee J, Hussain SR, Khanna S, Meenakshisundaram G, Kuppusamy P, Friedman A, Sen CK (2010) Hypoxia inducible microRNA 210 attenuates keratinocyte proliferation and impairs closure in a murine model of ischemic wounds. Proc Natl Acad Sci USA 107(15):6976–6981
Roy S, Biswas S, Khanna S, Gordillo G, Bergdall V, Green J, Marsh CB, Gould LJ, Sen CK (2009) Characterization of a preclinical model of chronic ischemic wound. Physiol Genomics 37(3):211–224
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
Weiler J, Hunziker J, Hall J (2006) Anti-miRNA oligonucleotides (amos): ammunition to target miRNAs implicated in human disease? Gene Ther 13(6):496–502
Roy S, Patel D, Khanna S, Gordillo GM, Biswas S, Friedman A, Sen CK (2007) Transcriptome-wide analysis of blood vessels laser captured from human skin and chronic wound-edge tissue. Proc Natl Acad Sci USA 104(36):14472–14477
Acknowledgments
Wound healing research in the author’s laboratory is funded by NIH awards GM 077185 and GM 069589 to CK Sen.
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Banerjee, J., Sen, C.K. (2013). MicroRNAs in Skin and Wound Healing. In: Ying, SY. (eds) MicroRNA Protocols. Methods in Molecular Biology, vol 936. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-083-0_26
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DOI: https://doi.org/10.1007/978-1-62703-083-0_26
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