Skip to main content
SpringerLink
Log in
SpringerLink
Log in

MicroRNAs: Novel Therapeutic Targets for Diabetic Wound Healing

  • Chapter
  • First Online:
The Diabetic Foot

Part of the book series: Contemporary Diabetes ((CDI))

Abstract

Diabetic foot ulcer (DFU) represents a major clinical challenge among diabetic complications and combines multiple physiological factors involved in the inhibition of wound healing. Healing of skin wounds is a complex and dynamic process in response to cutaneous injury, which involves a cascade of molecular events orchestrated with temporal and spatial gene regulation in different cell types. Abnormal patterns of tissue repair-related gene expression and resultant cellular malfunctions are key components of impaired healing in diabetic patients. Thus, to understand the pathophysiology of delayed healing in DFU, it is crucial to identify the functional regulators in individual cell types. Recent studies have demonstrated various genetic and epigenetic regulators of the cellular transcriptome and among them highly conserved, tiny noncoding RNAs, especially microRNAs, constitute an important class of master regulators to regulate diverse cellular functions essential for skin wound healing. Here, we will discuss the recent advancements on miRNA regulation of tissue repair processes and their potential as novel therapeutic targets to accelerate healing in diabetic patients.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 109.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 139.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Boulton AJ, Vileikyte L, Ragnarson-Tennvall G, Apelqvist J. The global burden of diabetic foot disease. Lancet. 2005;366(9498):1719–24.

    PubMed  Google Scholar 

  2. Brem H, Tomic-Canic M. Cellular and molecular basis of wound healing in diabetes. J Clin Invest. 2007;117(5):1219–22.

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Jeffcoate WJ, Harding KG. Diabetic foot ulcers. Lancet. 2003;361(9368):1545–51.

    PubMed  Google Scholar 

  4. Wang JM, Tao J, Chen DD, Cai JJ, Irani K, Wang Q, et al. MicroRNA miR-27b rescues bone marrow-derived angiogenic cell function and accelerates wound healing in type 2 diabetes mellitus. Arterioscler Thromb Vasc Biol. 2014;34(1):99–109.

    PubMed  Google Scholar 

  5. Barrientos S, Stojadinovic O, Golinko MS, Brem H, Tomic-Canic M. Growth factors and cytokines in wound healing. Wound Repair Regen. 2008;16(5):585–601.

    PubMed  Google Scholar 

  6. Dangwal S, Stratmann B, Bang C, Lorenzen JM, Kumarswamy R, Fiedler J, et al. Impairment of wound healing in patients with type 2 diabetes mellitus influences circulating MicroRNA patterns via inflammatory cytokines. Arterioscler Thromb Vasc Biol. 2015;35(6):1480–8.

    CAS  PubMed  Google Scholar 

  7. Dangwal S, Thum T. microRNA therapeutics in cardiovascular disease models. Annu Rev Pharmacol Toxicol. 2014;54:185–203.

    CAS  PubMed  Google Scholar 

  8. Bang C, Batkai S, Dangwal S, Gupta SK, Foinquinos A, Holzmann A, et al. Cardiac fibroblast-derived microRNA passenger strand-enriched exosomes mediate cardiomyocyte hypertrophy. J Clin Invest. 2014;124(5):2136–46.

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Icli B, Nabzdyk CS, Lujan-Hernandez J, Cahill M, Auster ME, Wara AK, et al. Regulation of impaired angiogenesis in diabetic dermal wound healing by microRNA-26a. J Mol Cell Cardiol. 2016;91:151–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Chan YC, Roy S, Khanna S, Sen CK. Downregulation of endothelial microRNA-200b supports cutaneous wound angiogenesis by desilencing GATA binding protein 2 and vascular endothelial growth factor receptor 2. Arterioscler Thromb Vasc Biol. 2012;32(6):1372–82.

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Ramirez HA, Liang L, Pastar I, Rosa AM, Stojadinovic O, Zwick TG, et al. Comparative genomic, MicroRNA, and tissue analyses reveal subtle differences between non-diabetic and diabetic foot skin. PLoS One. 2015;10(8):e0137133.

    PubMed  PubMed Central  Google Scholar 

  12. 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.

    PubMed  PubMed Central  Google Scholar 

  13. Beermann J, Piccoli MT, Viereck J, Thum T. Non-coding RNAs in development and disease: background, mechanisms, and therapeutic approaches. Physiol Rev. 2016;96(4):1297–325.

    CAS  PubMed  Google Scholar 

  14. ENCODE Project Consortium. An integrated encyclopedia of DNA elements in the human genome. Nature. 2012;489(7414):57–74.

    Google Scholar 

  15. Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell. 1993;75(5):843–54.

    CAS  PubMed  Google Scholar 

  16. Dangwal S, Schimmel K, Foinquinos A, Xiao K, Thum T. Noncoding RNAs in heart failure. Handb Exp Pharmacol. 2017;243:423–45.

    CAS  PubMed  Google Scholar 

  17. Jeck WR, Sorrentino JA, Wang K, Slevin MK, Burd CE, Liu J, et al. Circular RNAs are abundant, conserved, and associated with ALU repeats. RNA. 2013;19(2):141–57.

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116(2):281–97.

    CAS  PubMed  Google Scholar 

  19. Bartel DP. MicroRNAs: target recognition and regulatory functions. Cell. 2009;136(2):215–33.

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Grishok A, Pasquinelli AE, Conte D, Li N, Parrish S, Ha I, et al. Genes and mechanisms related to RNA interference regulate expression of the small temporal RNAs that control C. elegans developmental timing. Cell. 2001;106(1):23–34.

    CAS  PubMed  Google Scholar 

  21. Lee Y, Ahn C, Han J, Choi H, Kim J, Yim J, et al. The nuclear RNase III Drosha initiates microRNA processing. Nature. 2003;425(6956):415–9.

    CAS  PubMed  Google Scholar 

  22. Hutvagner G, Zamore PD. A microRNA in a multiple-turnover RNAi enzyme complex. Science. 2002;297(5589):2056–60.

    CAS  PubMed  Google Scholar 

  23. Mourelatos Z, Dostie J, Paushkin S, Sharma A, Charroux B, Abel L, et al. miRNPs: a novel class of ribonucleoproteins containing numerous microRNAs. Genes Dev. 2002;16(6):720–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  24. van Rooij E, Olson EN. MicroRNA therapeutics for cardiovascular disease: opportunities and obstacles. Nat Rev Drug Discov. 2012;11(11):860–72.

    PubMed  PubMed Central  Google Scholar 

  25. Kumarswamy R, Thum T. Non-coding RNAs in cardiac remodeling and heart failure. Circ Res. 2013;113(6):676–89.

    CAS  PubMed  Google Scholar 

  26. Krutzfeldt J, Kuwajima S, Braich R, Rajeev KG, Pena J, Tuschl T, et al. Specificity, duplex degradation and subcellular localization of antagomirs. Nucleic Acids Res. 2007;35(9):2885–92.

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Krutzfeldt J, Rajewsky N, Braich R, Rajeev KG, Tuschl T, Manoharan M, et al. Silencing of microRNAs in vivo with ‘antagomirs’. Nature. 2005;438(7068):685–9.

    PubMed  Google Scholar 

  28. Grunweller A, Hartmann RK. Locked nucleic acid oligonucleotides: the next generation of antisense agents? BioDrugs. 2007;21(4):235–43.

    PubMed  Google Scholar 

  29. Lanford RE, Hildebrandt-Eriksen ES, Petri A, Persson R, Lindow M, Munk ME, et al. Therapeutic silencing of microRNA-122 in primates with chronic hepatitis C virus infection. Science. 2010;327(5962):198–201.

    CAS  PubMed  Google Scholar 

  30. Elmen J, Lindow M, Silahtaroglu A, Bak M, Christensen M, Lind-Thomsen A, et al. Antagonism of microRNA-122 in mice by systemically administered LNA-antimiR leads to up-regulation of a large set of predicted target mRNAs in the liver. Nucleic Acids Res. 2008;36(4):1153–62.

    CAS  PubMed  Google Scholar 

  31. Bish LT, Morine K, Sleeper MM, Sanmiguel J, Wu D, Gao G, et al. Adeno-associated virus (AAV) serotype 9 provides global cardiac gene transfer superior to AAV1, AAV6, AAV7, and AAV8 in the mouse and rat. Hum Gene Ther. 2008;19(12):1359–68.

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Zincarelli C, Soltys S, Rengo G, Rabinowitz JE. Analysis of AAV serotypes 1-9 mediated gene expression and tropism in mice after systemic injection. Mol Ther. 2008;16(6):1073–80.

    CAS  PubMed  Google Scholar 

  33. Ni X, Zhang Y, Ribas J, Chowdhury WH, Castanares M, Zhang Z, et al. Prostate-targeted radiosensitization via aptamer-shRNA chimeras in human tumor xenografts. J Clin Invest. 2011;121(6):2383–90.

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Kondo T, Ishida Y. Molecular pathology of wound healing. Forensic Sci Int. 2010;203(1–3):93–8.

    CAS  PubMed  Google Scholar 

  35. Hocking AM, Gibran NS. Mesenchymal stem cells: paracrine signaling and differentiation during cutaneous wound repair. Exp Cell Res. 2010;316(14):2213–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Falanga V. Wound healing and its impairment in the diabetic foot. Lancet. 2005;366(9498):1736–43.

    PubMed  Google Scholar 

  37. Li J, Chen J, Kirsner R. Pathophysiology of acute wound healing. Clin Dermatol. 2007;25(1):9–18.

    CAS  PubMed  Google Scholar 

  38. Park LK, Maione AG, Smith A, Gerami-Naini B, Iyer LK, Mooney DJ, et al. Genome-wide DNA methylation analysis identifies a metabolic memory profile in patient-derived diabetic foot ulcer fibroblasts. Epigenetics. 2014;9(10):1339–49.

    PubMed  PubMed Central  Google Scholar 

  39. Maione AG, Brudno Y, Stojadinovic O, Park LK, Smith A, Tellechea A, et al. Three-dimensional human tissue models that incorporate diabetic foot ulcer-derived fibroblasts mimic in vivo features of chronic wounds. Tissue Eng Part C Methods. 2015;21(5):499–508.

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Liang L, Stone RC, Stojadinovic O, Ramirez H, Pastar I, Maione AG, et al. Integrative analysis of miRNA and mRNA paired expression profiling of primary fibroblast derived from diabetic foot ulcers reveals multiple impaired cellular functions. Wound Repair Regen. 2016;24(6):943–53.

    PubMed  PubMed Central  Google Scholar 

  41. Polytarchou C, Iliopoulos D, Hatziapostolou M, Kottakis F, Maroulakou I, Struhl K, et al. Akt2 regulates all Akt isoforms and promotes resistance to hypoxia through induction of miR-21 upon oxygen deprivation. Cancer Res. 2011;71(13):4720–31.

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Shi B, Sepp-Lorenzino L, Prisco M, Linsley P, deAngelis T, Baserga R. Micro RNA 145 targets the insulin receptor substrate-1 and inhibits the growth of colon cancer cells. J Biol Chem. 2007;282(45):32582–90.

    CAS  PubMed  Google Scholar 

  43. Thum T, Gross C, Fiedler J, Fischer T, Kissler S, Bussen M, et al. MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts. Nature. 2008;456(7224):980–4.

    CAS  PubMed  Google Scholar 

  44. Oh J, Takahashi R, Kondo S, Mizoguchi A, Adachi E, Sasahara RM, et al. The membrane-anchored MMP inhibitor RECK is a key regulator of extracellular matrix integrity and angiogenesis. Cell. 2001;107(6):789–800.

    CAS  PubMed  Google Scholar 

  45. Davis-Dusenbery BN, Chan MC, Reno KE, Weisman AS, Layne MD, Lagna G, et al. Down-regulation of Kruppel-like factor-4 (KLF4) by microRNA-143/145 is critical for modulation of vascular smooth muscle cell phenotype by transforming growth factor-beta and bone morphogenetic protein 4. J Biol Chem. 2011;286(32):28097–110.

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Wang Y, Hu C, Cheng J, Chen B, Ke Q, Lv Z, et al. MicroRNA-145 suppresses hepatocellular carcinoma by targeting IRS1 and its downstream Akt signaling. Biochem Biophys Res Commun. 2014;446(4):1255–60.

    CAS  PubMed  Google Scholar 

  47. Kong L, Zhu J, Han W, Jiang X, Xu M, Zhao Y, et al. Significance of serum microRNAs in pre-diabetes and newly diagnosed type 2 diabetes: a clinical study. Acta Diabetol. 2011;48(1):61–9.

    CAS  PubMed  Google Scholar 

  48. Harper RA, Grove G. Human skin fibroblasts derived from papillary and reticular dermis: differences in growth potential in vitro. Science. 1979;204(4392):526–7.

    CAS  PubMed  Google Scholar 

  49. Sorrell JM, Baber MA, Caplan AI. Site-matched papillary and reticular human dermal fibroblasts differ in their release of specific growth factors/cytokines and in their interaction with keratinocytes. J Cell Physiol. 2004;200(1):134–45.

    CAS  PubMed  Google Scholar 

  50. Chen JX, Chen Y, DeBusk L, Lin W, Lin PC. Dual functional roles of Tie-2/angiopoietin in TNF-alpha-mediated angiogenesis. Am J Physiol Heart Circ Physiol. 2004;287(1):H187–95.

    CAS  PubMed  Google Scholar 

  51. Sainson RC, Johnston DA, Chu HC, Holderfield MT, Nakatsu MN, Crampton SP, et al. TNF primes endothelial cells for angiogenic sprouting by inducing a tip cell phenotype. Blood. 2008;111(10):4997–5007.

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Pase L, Layton JE, Kloosterman WP, Carradice D, Waterhouse PM, Lieschke GJ. miR-451 regulates zebrafish erythroid maturation in vivo via its target gata2. Blood. 2009;113(8):1794–804.

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Fiedler J, Jazbutyte V, Kirchmaier BC, Gupta SK, Lorenzen J, Hartmann D, et al. MicroRNA-24 regulates vascularity after myocardial infarction. Circulation. 2011;124(6):720–30.

    CAS  PubMed  Google Scholar 

  54. Kim T, Veronese A, Pichiorri F, Lee TJ, Jeon YJ, Volinia S, et al. p53 regulates epithelial-mesenchymal transition through microRNAs targeting ZEB1 and ZEB2. J Exp Med. 2011;208(5):875–83.

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Kane CD, Greenhalgh DG. Expression and localization of p53 and bcl-2 in healing wounds in diabetic and nondiabetic mice. Wound Repair Regen. 2000;8(1):45–58.

    CAS  PubMed  Google Scholar 

  56. Yang Y, Ahn YH, Gibbons DL, Zang Y, Lin W, Thilaganathan N, et al. The Notch ligand Jagged2 promotes lung adenocarcinoma metastasis through a miR-200-dependent pathway in mice. J Clin Invest. 2011;121(4):1373–85.

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Zampetaki A, Kiechl S, Drozdov I, Willeit P, Mayr U, Prokopi M, et al. Plasma microRNA profiling reveals loss of endothelial miR-126 and other microRNAs in type 2 diabetes. Circ Res. 2010;107(6):810–7.

    CAS  PubMed  Google Scholar 

  58. Nagpal N, Kulshreshtha R. miR-191: an emerging player in disease biology. Front Genet. 2014;5:99.

    PubMed  PubMed Central  Google Scholar 

  59. Kiezun A, Artzi S, Modai S, Volk N, Isakov O, Shomron N. miRviewer: a multispecies microRNA homologous viewer. BMC Res Notes. 2012;5:92. https://doi.org/10.1186/1756-0500-5-92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Hergenreider E, Heydt S, Treguer K, Boettger T, Horrevoets AJ, Zeiher AM, et al. Atheroprotective communication between endothelial cells and smooth muscle cells through miRNAs. Nat Cell Biol. 2012;14(3):249–56.

    CAS  PubMed  Google Scholar 

  61. Gupta SK, Bang C, Thum T. Circulating microRNAs as biomarkers and potential paracrine mediators of cardiovascular disease. Circ Cardiovasc Genet. 2010;3(5):484–8.

    CAS  PubMed  Google Scholar 

  62. Taliana L, Benezra M, Greenberg RS, Masur SK, Bernstein AM. ZO-1: lamellipodial localization in a corneal fibroblast wound model. Invest Ophthalmol Vis Sci. 2005;46(1):96–103.

    PubMed  Google Scholar 

  63. Katsuno T, Umeda K, Matsui T, Hata M, Tamura A, Itoh M, et al. Deficiency of zonula occludens-1 causes embryonic lethal phenotype associated with defected yolk sac angiogenesis and apoptosis of embryonic cells. Mol Biol Cell. 2008;19(6):2465–75.

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Goumans MJ, Valdimarsdottir G, Itoh S, Rosendahl A, Sideras P, ten Dijke P. Balancing the activation state of the endothelium via two distinct TGF-beta type I receptors. EMBO J. 2002;21(7):1743–53.

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Norton JD, Deed RW, Craggs G, Sablitzky F. Id helix-loop-helix proteins in cell growth and differentiation. Trends Cell Biol. 1998;8(2):58–65.

    CAS  PubMed  Google Scholar 

  66. Chen L, Wu F, Xia WH, Zhang YY, Xu SY, Cheng F, et al. CXCR4 gene transfer contributes to in vivo reendothelialization capacity of endothelial progenitor cells. Cardiovasc Res. 2010;88(3):462–70.

    CAS  PubMed  Google Scholar 

  67. Bang C, Fiedler J, Thum T. Cardiovascular importance of the microRNA-23/27/24 family. Microcirculation. 2012;19(3):208–14.

    CAS  PubMed  Google Scholar 

  68. Zhou Q, Gallagher R, Ufret-Vincenty R, Li X, Olson EN, Wang S. Regulation of angiogenesis and choroidal neovascularization by members of microRNA-23~27~24 clusters. Proc Natl Acad Sci U S A. 2011;108(20):8287–92.

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Usui ML, Underwood RA, Mansbridge JN, Muffley LA, Carter WG, Olerud JE. Morphological evidence for the role of suprabasal keratinocytes in wound reepithelialization. Wound Repair Regen. 2005;13(5):468–79.

    PubMed  Google Scholar 

  70. Ridley AJ, Schwartz MA, Burridge K, Firtel RA, Ginsberg MH, Borisy G, et al. Cell migration: integrating signals from front to back. Science. 2003;302(5651):1704–9.

    CAS  PubMed  Google Scholar 

  71. Sundaram GM, Common JE, Gopal FE, Srikanta S, Lakshman K, Lunny DP, et al. ‘See-saw’ expression of microRNA-198 and FSTL1 from a single transcript in wound healing. Nature. 2013;495(7439):103–6.

    CAS  PubMed  Google Scholar 

  72. Jin Y, Tymen SD, Chen D, Fang ZJ, Zhao Y, Dragas D, et al. MicroRNA-99 family targets AKT/mTOR signaling pathway in dermal wound healing. PLoS One. 2013;8(5):e64434.

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Hildebrand J, Rutze M, Walz N, Gallinat S, Wenck H, Deppert W, et al. A comprehensive analysis of microRNA expression during human keratinocyte differentiation in vitro and in vivo. J Invest Dermatol. 2011;131(1):20–9.

    CAS  PubMed  Google Scholar 

  74. van Solingen C, Araldi E, Chamorro-Jorganes A, Fernandez-Hernando C, Suarez Y. Improved repair of dermal wounds in mice lacking microRNA-155. J Cell Mol Med. 2014;18(6):1104–12.

    PubMed  PubMed Central  Google Scholar 

  75. de Boer HC, van Solingen C, Prins J, Duijs JM, Huisman MV, Rabelink TJ, et al. Aspirin treatment hampers the use of plasma microRNA-126 as a biomarker for the progression of vascular disease. Eur Heart J. 2013;34(44):3451–7.

    PubMed  Google Scholar 

  76. Lankisch TO, Voigtlander T, Manns MP, Holzmann A, Dangwal S, Thum T. MicroRNAs in the bile of patients with biliary strictures after liver transplantation. Liver Transpl. 2014;20(6):673–8.

    PubMed  Google Scholar 

  77. Osipova J, Fischer DC, Dangwal S, Volkmann I, Widera C, Schwarz K, et al. Diabetes-associated microRNAs in pediatric patients with type 1 diabetes mellitus: a cross-sectional cohort study. J Clin Endocrinol Metab. 2014;99(9):E1661–5.

    CAS  PubMed  Google Scholar 

  78. Gidlof O, van der Brug M, Ohman J, Gilje P, Olde B, Wahlestedt C, et al. Platelets activated during myocardial infarction release functional miRNA, which can be taken up by endothelial cells and regulate ICAM1 expression. Blood. 2013;121(19):3908–17. S1-26

    PubMed  Google Scholar 

  79. Willeit P, Zampetaki A, Dudek K, Kaudewitz D, King A, Kirkby NS, et al. Circulating microRNAs as novel biomarkers for platelet activation. Circ Res. 2013;112(4):595–600.

    CAS  PubMed  Google Scholar 

  80. Zernecke A, Bidzhekov K, Noels H, Shagdarsuren E, Gan L, Denecke B, et al. Delivery of microRNA-126 by apoptotic bodies induces CXCL12-dependent vascular protection. Sci Signal. 2009;2(100):ra81.

    PubMed  Google Scholar 

  81. Dangwal S, Thum T. MicroRNAs in platelet physiology and pathology. Hamostaseologie. 2013;33(1):17–20.

    CAS  PubMed  Google Scholar 

  82. Dangwal S, Thum T. MicroRNAs in platelet biogenesis and function. Thromb Haemost. 2012;108(4):599–604.

    CAS  PubMed  Google Scholar 

  83. Hatziapostolou M, Polytarchou C, Aggelidou E, Drakaki A, Poultsides GA, Jaeger SA, et al. An HNF4alpha-miRNA inflammatory feedback circuit regulates hepatocellular oncogenesis. Cell. 2011;147(6):1233–47.

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Creasey KM, Zhai J, Borges F, Van Ex F, Regulski M, Meyers BC, et al. miRNAs trigger widespread epigenetically activated siRNAs from transposons in Arabidopsis. Nature. 2014;508(7496):411–5.

    CAS  PubMed  PubMed Central  Google Scholar 

  85. Janssen HL, Reesink HW, Lawitz EJ, Zeuzem S, Rodriguez-Torres M, Patel K, et al. Treatment of HCV infection by targeting microRNA. N Engl J Med. 2013;368(18):1685–94.

    CAS  PubMed  Google Scholar 

  86. van der Ree MH, van der Meer AJ, de Bruijne J, Maan R, van Vliet A, Welzel TM, et al. Long-term safety and efficacy of microRNA-targeted therapy in chronic hepatitis C patients. Antivir Res. 2014;111:53–9.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Surgery, Beth Israel Deaconess Medical Centre, Boston, MA, USA

    Seema Dangwal MPharm, PhD

  2. Institute of Molecular and Translational Therapeutic Strategies, Medical School Hannover, Hannover, Germany

    Seema Dangwal MPharm, PhD, Ariana Foinquinos PhD & Thomas Thum MD, PhD

Authors
  1. Seema Dangwal MPharm, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ariana Foinquinos PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Thomas Thum MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Seema Dangwal MPharm, PhD .

Editor information

Editors and Affiliations

  1. Rongxiang Xu, MD, Professor of Surgery, Harvard Medical School Director, The Rongxiang Xu, MD, Center for Regenerative Therapeutics Research Director, Joslin-Beth Israel Deaconess Foot Center Beth Israel Deaconess Medical Center, Boston, MA, USA

    Aristidis Veves

  2. Chief, Division of Podiatry, Beth Israel Deaconess Medical Center, Associate Professor of Surgery, Harvard Medical School, Co-director, Joslin-Bl Deaconess Diabetic Foot Center Consultant, Joslin Diabetes Center, Boston, MA, USA

    John M. Giurini

  3. Associate Professor of Surgery, Harvard Medical School, Division of Vascular and Endovascular Surgery, Beth Israel Deaconess Medical Center, Joslin Diabetes Center, Boston, MA, USA

    Raul J. Guzman

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer International Publishing AG, part of Springer Nature

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Dangwal, S., Foinquinos, A., Thum, T. (2018). MicroRNAs: Novel Therapeutic Targets for Diabetic Wound Healing. In: Veves, A., Giurini, J., Guzman, R. (eds) The Diabetic Foot. Contemporary Diabetes. Humana, Cham. https://doi.org/10.1007/978-3-319-89869-8_14

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-89869-8_14

  • Published:

  • Publisher Name: Humana, Cham

  • Print ISBN: 978-3-319-89868-1

  • Online ISBN: 978-3-319-89869-8

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation