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MicroRNAs in injury and repair

Abstract

Organ damage and resulting pathologies often involve multiple deregulated pathways. MicroRNAs (miRNAs) are short, non-coding RNAs that regulate a multitude of genes at the post-transcriptional level. Since their discovery over two decades ago, miRNAs have been established as key players in the molecular mechanisms of mammalian biology including the maintenance of normal homeostasis and the regulation of disease pathogenesis. In recent years, there has been substantial progress in innovative techniques to measure miRNAs along with advances in targeted delivery of agents modulating their expression. This has expanded the scope of miRNAs from being important mediators of cell signaling to becoming viable quantitative biomarkers and therapeutic targets. Currently, miRNA therapeutics are in clinical trials for multiple disease areas and vast numbers of patents have been filed for miRNAs involved in various pathological states. In this review, we summarize miRNAs involved in organ injury and repair, specifically with regard to organs that are the most susceptible to injury: the liver, heart and kidney. In addition, we review the current state of knowledge on miRNA biology, miRNA biomarkers and nucleotide-based therapeutics designed to target miRNAs to prevent organ injury and promote repair.

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References

  • Adachi T et al (2010) Plasma microRNA 499 as a biomarker of acute myocardial infarction. Clin Chem 56(7):1183–1185

    CAS  PubMed  Article  Google Scholar 

  • Aguirre A et al (2014) In vivo activation of a conserved microRNA program induces mammalian heart regeneration. Cell Stem Cell 15(5):589–604

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • Ai J et al (2010) Circulating microRNA-1 as a potential novel biomarker for acute myocardial infarction. Biochem Biophys Res Commun 391(1):73–77

    CAS  PubMed  Article  Google Scholar 

  • Anglicheau D et al (2009) MicroRNA expression profiles predictive of human renal allograft status. Proc Natl Acad Sci USA 106(13):5330–5335

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • Bala S et al. (2012) Circulating microRNAs in exosomes indicate hepatocyte injury and inflammation in alcoholic, drug-induced, and inflammatory liver diseases. Hepatology (Baltimore, Md.) 56(5): 1946–1957

  • Bandiera S et al (2015) miR-122—a key factor and therapeutic target in liver disease. J Hepatol 62(2):448–457

    CAS  PubMed  Article  Google Scholar 

  • Beavers KR, Nelson CE, Duvall CL (2015) MiRNA inhibition in tissue engineering and regenerative medicine. Adv Drug Deliv Rev 88:123–137

    CAS  PubMed  Article  Google Scholar 

  • Bei Y et al (2016) miR-382 targeting PTEN-Akt axis promotes liver regeneration. Oncotarget 7(2):1584–1597

    PubMed  Article  Google Scholar 

  • Ben-Dov IZ et al (2012) MicroRNA sequence profiles of human kidney allografts with or without tubulointerstitial fibrosis. Transplantation 94(11):1086–1094

    CAS  PubMed  Article  Google Scholar 

  • Bergmann O et al (2009) Evidence for cardiomyocyte renewal in humans. Science 324(5923):98–102

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • Bhatt K et al (2015) MicroRNA-687 induced by hypoxia-inducible factor-1 targets phosphatase and tensin homolog in renal ischemia-reperfusion injury. J Am Soc Nephrol JASN 26(7):1588–1596

    CAS  PubMed  Article  Google Scholar 

  • Bhatt K et al (2010) MicroRNA-34a is induced via p53 during cisplatin nephrotoxicity and contributes to cell survival. Mol Med (Cambridge, Mass.) 16(9–10):409–416

  • Bijkerk R et al (2016) Silencing of microRNA-132 reduces renal fibrosis by selectively inhibiting myofibroblast proliferation. Kidney Int 89(6):1268–1280

    CAS  PubMed  Article  Google Scholar 

  • Bonventre JV (2014) Primary proximal tubule injury leads to epithelial cell cycle arrest, fibrosis, vascular rarefaction, and glomerulosclerosis. Kidney Int Suppl 4(1):39–44

    CAS  Article  Google Scholar 

  • Boon RA et al (2013) MicroRNA-34a regulates cardiac ageing and function. Nature 495(7439):107–110

    CAS  PubMed  Article  Google Scholar 

  • Bostjancic E, Zidar N, Stajer D, Glavac D (2009) MicroRNAs miR-1, miR-133a, miR-133b and miR-208 are dysregulated in human myocardial infarction. Cardiology 115(3):163–169

    PubMed  Article  CAS  Google Scholar 

  • Bouchie A (2013) First microRNA mimic enters clinic. Nat Biotechnol 31(7):577

    CAS  PubMed  Article  Google Scholar 

  • Breving K, Esquela-Kerscher A (2010) The complexities of microRNA regulation: mirandering around the rules. Int J Biochem Cell Biol 42(8):1316–1329

    CAS  PubMed  Article  Google Scholar 

  • Brümmer A, Hausser J (2014) MicroRNA binding sites in the coding region of mRNAs: extending the repertoire of post-transcriptional gene regulation. BioEssays: News Rev Mol Cell Dev Biol 36(6):617–626

    Article  CAS  Google Scholar 

  • Callis TE et al (2009) MicroRNA-208a is a regulator of cardiac hypertrophy and conduction in mice. J Clin Investig 119(9):2772–2786

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • Castro RE et al (2013) miR-34a/SIRT1/p53 is suppressed by ursodeoxycholic acid in the rat liver and activated by disease severity in human non-alcoholic fatty liver disease. J Hepatol 58(1):119–125

    CAS  PubMed  Article  Google Scholar 

  • Chan YC et al (2012) 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 32(6):1372–1382

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • Chau BN et al (2012) MicroRNA-21 promotes fibrosis of the kidney by silencing metabolic pathways. Sci Transl Med 4(121):1–12

    Article  CAS  Google Scholar 

  • Chen JF et al (2006) The role of microRNA-1 and microRNA-133 in skeletal muscle proliferation and differentiation. Nature 38(2):228–233

    CAS  Google Scholar 

  • Chen H et al (2011) Mir-34a is upregulated during liver regeneration in rats and is associated with the suppression of hepatocyte proliferation. PLoS One 6(5):1–7

    Google Scholar 

  • Chen J et al (2013) mir-17-92 cluster is required for and sufficient to induce cardiomyocyte proliferation in postnatal and adult hearts. Circ Res 112(12):1557–1566

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • Cheung O et al (2008) Nonalcoholic steatohepatitis is associated with altered hepatic MicroRNA expression. Hepatology 48(6):1810–1820

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • Christopher AF et al (2016) MicroRNA therapeutics: discovering novel targets and developing specific therapy. Perspect Clin Res 7(2):68–74

    PubMed  PubMed Central  Article  Google Scholar 

  • Church RJ et al (2015) Beyond miR-122: identification of microRNA alterations in blood during a time course of hepatobiliary injury and biliary hyperplasia in rats. Toxicol Sci 150(1):3–14

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  • clinicaltrials.gov. Study of Weekly RG-012 injections in patients with Alport syndrome (HERA). 2016; Available from: https://clinicaltrials.gov/ct2/show/NCT02855268?term=rg-012&rank=1

  • Corsten MF et al (2010) Circulating MicroRNA-208b and MicroRNA-499 reflect myocardial damage in cardiovascular disease. Circ Cardiovasc Genet 3(6):499–506

    PubMed  Article  Google Scholar 

  • Cui R et al (2016) Global miRNA expression is temporally correlated with acute kidney injury in mice. PeerJ 4:1–16

    Google Scholar 

  • da Costa Martins PA et al (2008) Conditional dicer gene deletion in the postnatal myocardium provokes spontaneous cardiac remodeling. Circulation 118(15):1567–1576

    PubMed  Article  CAS  Google Scholar 

  • de Alwis NM, Day CP (2008) Non-alcoholic fatty liver disease: the mist gradually clears. J Hepatol 48:S104–S112

    PubMed  Article  CAS  Google Scholar 

  • Dear JW et al (2014) Early detection of paracetamol toxicity using circulating liver microRNA and markers of cell necrosis. Br J Clin Pharmacol 77(5):904–905

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • Desai VG et al (2014) Early biomarkers of doxorubicin-induced heart injury in a mouse model. Toxicol Appl Pharmacol 281(2):221–229

    CAS  PubMed  Article  Google Scholar 

  • Ding XC, Weiler J, Grosshans H (2009) Regulating the regulators: mechanisms controlling the maturation of microRNAs. Trends Biotechnol 27(1):27–36

    CAS  PubMed  Article  Google Scholar 

  • Ding J et al (2015) Effect of miR-34a in regulating steatosis by targeting PPARα expression in nonalcoholic fatty liver disease. Sci Rep 5(13729):1–10

    Google Scholar 

  • Du P et al (2015) A biogenesis step upstream of microprocessor controls miR-17 ~ 92 expression. Cell 162(4):885–899

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • D’Alessandra Y et al (2010) Circulating microRNAs are new and sensitive biomarkers of myocardial infarction. Eur Heart J 31(22):2765–2773

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  • Ferreira DM et al (2014) c-Jun N-terminal kinase 1/c-Jun activation of the p53/microRNA 34a/sirtuin 1 pathway contributes to apoptosis induced by deoxycholic acid in rat liver. Mol Cell Biol 34(6):1100–1120

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  • Fornari F et al (2008) MiR-221 controls CDKN1C/p57 and CDKN1B/p27 expression in human hepatocellular carcinoma. Oncogene 27(43):5651–5661

    CAS  PubMed  Article  Google Scholar 

  • Fromm B et al (2015) A uniform system for the annotation of vertebrate microRNA genes and the evolution of the human microRNAome. Annu Rev Genet 49:213–242

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • Ge X-TT et al (2014) miR-21 improves the neurological outcome after traumatic brain injury in rats. Sci Rep 4(6718):1–11

    Google Scholar 

  • Gebert LF et al (2014) Miravirsen (SPC3649) can inhibit the biogenesis of miR-122. Nucl Acids Res 42(1):609–621

    CAS  PubMed  Article  Google Scholar 

  • Glass C, Singla DK (2011) MicroRNA-1 transfected embryonic stem cells enhance cardiac myocyte differentiation and inhibit apoptosis by modulating the PTEN/Akt pathway in the infarcted heart. Am J Physiol-Heart Circ Physiol 301(5):H2038–H2049. doi:10.1152/ajpheart.00271.2011

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • Glowacki F et al (2013) Increased circulating miR-21 levels are associated with kidney fibrosis. PLoS One 8(2):1–11

    Article  CAS  Google Scholar 

  • Gomez IG et al (2015) Anti-microRNA-21 oligonucleotides prevent Alport nephropathy progression by stimulating metabolic pathways. J Clin Investig 125(1):141–156

    PubMed  Article  Google Scholar 

  • Griffiths-Jones S, Saini HK, van Dongen (2008) miRBase: tools for microRNA genomics. Nucl Acids 36:D154–D158

    CAS  Article  Google Scholar 

  • Guo Z et al (2013) Antisense oligonucleotide treatment enhances the recovery of acute lung injury through IL-10-secreting M2-like macrophage-induced expansion of CD4 + regulatory T cells. J Immunol (Baltimore, Md.: 1950) 190(8):4337–4348

  • Hand NJ et al (2009) Hepatic function is preserved in the absence of mature microRNAs. Hepatology 49(2):618–626

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • Harrill AH et al (2016) MicroRNA biomarkers of toxicity in biological matrices. Toxicol Sci 152(2):264–272

    CAS  PubMed  Article  Google Scholar 

  • Heidersbach A et al (2013) microRNA-1 regulates sarcomere formation and suppresses smooth muscle gene expression in the mammalian heart. eLife 2(e01323):1–22

    Google Scholar 

  • Hennino M-F et al (2016) miR-21-5p renal expression is associated with fibrosis and renal survival in patients with IgA nephropathy. Sci Rep 6(27209):1–9

    Google Scholar 

  • Ho J et al (2008) Podocyte-specific loss of functional microRNAs leads to rapid glomerular and tubular injury. J Am Soc Nephrol: JASN 19(11):2069–2075

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • Hodgkinson CP et al (2015) MicroRNAs and cardiac regeneration. Circ Res 116(10):1700–1711

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • Hsu S-HH et al (2012) Essential metabolic, anti-inflammatory, and anti-tumorigenic functions of miR-122 in liver. J Clin Investig 122(8):2871–2883

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • Hsu A et al (2014) Systemic approach to identify serum microRNAs as potential biomarkers for acute myocardial infarction. Biomed Res Int 2014(418628):1–13

    Google Scholar 

  • Hu J et al (2013) Plasma microRNA, a potential biomarker for acute rejection after liver transplantation. Transplantation 95(8):991–999

    CAS  PubMed  Article  Google Scholar 

  • Hullinger TG et al (2012) Inhibition of miR-15 protects against cardiac ischemic injury. Circ Res 110(1):71–81

    CAS  PubMed  Article  Google Scholar 

  • Huntzinger E, Izaurralde E (2011) Gene silencing by microRNAs: contributions of translational repression and mRNA decay. Nat Rev Genet 12(2):99–110

    CAS  PubMed  Article  Google Scholar 

  • Ivey KN et al (2008) MicroRNA regulation of cell lineages in mouse and human embryonic stem cells. Cell Stem Cell 2(3):219–229

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • Janssen HL et al (2013) Treatment of HCV infection by targeting microRNA. N Engl J Med 368(18):1685–1694

    CAS  PubMed  Article  Google Scholar 

  • Jayawardena TM et al (2012) MicroRNA-mediated in vitro and in vivo direct reprogramming of cardiac fibroblasts to cardiomyocytes. Circ Res 110(11):1465–1473

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • Jenkins RH et al (2012) Transforming growth factor β1 represses proximal tubular cell microRNA-192 expression through decreased hepatocyte nuclear factor DNA binding. Biochem J 443(2):407–416

    CAS  PubMed  Article  Google Scholar 

  • Jopling C et al (2010) Zebrafish heart regeneration occurs by cardiomyocyte dedifferentiation and proliferation. Nature 464(7288):606–609

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • Kang YJ (2001) Molecular and cellular mechanisms of cardiotoxicity. Environ Health Perspect 109(Suppl 1):27–34

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • Kanki M et al (2014) Identification of urinary miRNA biomarkers for detecting cisplatin-induced proximal tubular injury in rats. Toxicology 324:158–168

    CAS  PubMed  Article  Google Scholar 

  • Kobayashi A et al (2008) Six2 defines and regulates a multipotent self-renewing nephron progenitor population throughout mammalian kidney development. Cell Stem Cell 3(2):169–181

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • Köberle V, Waidmann O, Kronenberger B (2013) Serum microRNA-122 kinetics in patients with chronic hepatitis C virus infection during antiviral therapy. J Viral Hepat 20(8):530–535

    PubMed  Article  Google Scholar 

  • Koturbash I et al (2015) microRNAs as pharmacogenomic biomarkers for drug efficacy and drug safety assessment. Biomark Med 9(11):1153–1176

    CAS  PubMed  Article  Google Scholar 

  • Krauskopf J et al (2015) Application of high-throughput sequencing to circulating microRNAs reveals novel biomarkers for drug-induced liver injury. Toxicol Sci 143(2):268–276

    CAS  PubMed  Article  Google Scholar 

  • Lameire NH et al (2013) Acute kidney injury: an increasing global concern. Lancet (London, England) 382(9887): 170–179

  • Lan Y-FF et al (2012) MicroRNA-494 reduces ATF3 expression and promotes AKI. J of the Am Soc Nephrol JASN 23(12):2012–2023

    CAS  Article  Google Scholar 

  • Laterza OF et al (2009) Plasma MicroRNAs as sensitive and specific biomarkers of tissue injury. Clin Chem 55(11):1977–1983

    CAS  PubMed  Article  Google Scholar 

  • Lee WM (2003) Drug-induced hepatotoxicity. N Engl J Med 349(5):474–485

    CAS  PubMed  Article  Google Scholar 

  • Lee WM (2008) Etiologies of acute liver failure. Semin Liver Dis 28(2):142–152

    PubMed  Article  Google Scholar 

  • Li D et al (2015a) MicroRNA-31 promotes skin wound healing by enhancing keratinocyte proliferation and migration. J Invest Dermatol 135(6):1676–1685

    CAS  PubMed  Article  Google Scholar 

  • Li D et al (2015b) MicroRNA-132 enhances transition from inflammation to proliferation during wound healing. J Clin Investig 125(8):3008–3026

    PubMed  PubMed Central  Article  Google Scholar 

  • Li Z, Rana TM (2014) Therapeutic targeting of microRNAs: current status and future challenges. Nat Rev Drug Discov 13(8):622–638

    CAS  PubMed  Article  Google Scholar 

  • Liu N, Bezprozvannaya S, Williams AH (2008) microRNA-133a regulates cardiomyocyte proliferation and suppresses smooth muscle gene expression in the heart. Genes Dev 22(23):3242–3254

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • Liu L et al (2014) miR-208a as a biomarker of isoproterenol-induced cardiac injury in Sod2 ± and C57BL/6 J wild-type mice. Toxicol Pathol 42(7):1117–1129

    CAS  PubMed  Article  Google Scholar 

  • Liu X-JJ et al (2015a) MicroRNA-34a suppresses autophagy in tubular epithelial cells in acute kidney injury. Am J Nephrol 42(2):168–175

    CAS  PubMed  Article  Google Scholar 

  • Liu D et al (2015b) Administration of Antagomir-223 inhibits apoptosis, promotes angiogenesis and functional recovery in rats with spinal cord injury. Cell Mol Neurobiol 35(4):483–491

    CAS  PubMed  Article  Google Scholar 

  • Lorenzen JM et al (2014) MicroRNA-24 antagonism prevents renal ischemia reperfusion injury. J Am Soc Nephrol JASN 25(12):2717–2729

    CAS  PubMed  Article  Google Scholar 

  • Mall C et al (2013) Stability of miRNA in human urine supports its biomarker potential. Biomark Med 7(4):623–631

    CAS  PubMed  Article  Google Scholar 

  • Marco A, Ninova M, Griffiths-Jones S (2013) Multiple products from microRNA transcripts. Biochem Soc Trans 41(4):850–854

    CAS  PubMed  Article  Google Scholar 

  • Marquez RT, Wendlandt E, Galle CS (2010) MicroRNA-21 is upregulated during the proliferative phase of liver regeneration, targets Pellino-1, and inhibits NF-κB signaling. Am J Physiol-Gastrointest Liver Physiol 298(4):G535–G541

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • Marrone AK et al (2014) MicroRNA-17 ~ 92 is required for nephrogenesis and renal function. J Am Soc Nephrol: JASN 25(7):1440–1452

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • Matsumoto S et al (2013) Circulating p53-responsive microRNAs are predictive indicators of heart failure after acute myocardial infarction. Circ Res 113(3):322–326

    CAS  PubMed  Article  Google Scholar 

  • Meer AJ, Farid WRR, Sonneveld MJ (2013) Sensitive detection of hepatocellular injury in chronic hepatitis C patients with circulating hepatocyte-derived microRNA-122. J Viral Hepat 20(3):158–166

    PubMed  Article  Google Scholar 

  • Michalopoulos G, DeFrances M (1997) Liver regeneration. Science 276(5309):60–66

    CAS  PubMed  Article  Google Scholar 

  • Miyaaki H et al (2014) Significance of serum and hepatic microRNA-122 levels in patients with non-alcoholic fatty liver disease. Liver Int 34(7):e302–e307

    CAS  PubMed  Article  Google Scholar 

  • Mogilyansky E, Rigoutsos I (2013) The miR-17/92 cluster: a comprehensive update on its genomics, genetics, functions and increasingly important and numerous roles in health and disease. Cell Death Differ 20(12):1604–1614

    Article  CAS  Google Scholar 

  • Mohd Hanafiah K et al (2013) Global epidemiology of hepatitis C virus infection: new estimates of age-specific antibody to HCV seroprevalence. Hepatology (Baltimore, MD) 57(4):1333–1342

    Article  Google Scholar 

  • Montgomery RL et al (2011) Therapeutic inhibition of miR-208a improves cardiac function and survival during heart failure. Circulation 124(14):1537–1547

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • Nagalakshmi VK et al (2011) Dicer regulates the development of nephrogenic and ureteric compartments in the mammalian kidney. Kidney Int 79(3):317–330

    CAS  PubMed  Article  Google Scholar 

  • Nagano T et al (2013) Liver-specific microRNAs as biomarkers of nanomaterial-induced liver damage. Nanotechnology 24:1–7

    Article  CAS  Google Scholar 

  • Ng R et al (2012) A microRNA-21 surge facilitates rapid cyclin D1 translation and cell cycle progression in mouse liver regeneration. J Clin Invest 122(3):1097–1108

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • Ninomiya M et al (2016) The expression of miR-125b-5p is increased in the serum of patients with chronic hepatitis B infection and inhibits the detection of hepatitis B virus surface antigen. J Viral Hepatitis 23(5):330–339

    CAS  Article  Google Scholar 

  • Nishimura Y et al (2015) Plasma miR-208 as a useful biomarker for drug-induced cardiotoxicity in rats. J Appl Toxicol JAT 35(2):173–180

    CAS  PubMed  Article  Google Scholar 

  • Oberpriller JO, Oberpriller JC (1974) Response of the adult newt ventricle to injury. J Exp Zool 187(2):249–253

    CAS  PubMed  Article  Google Scholar 

  • Oliveira-Carvalho V, Carvalho VO, Bocchi EA (2013) The emerging role of miR-208a in the heart. DNA Cell Biol 32(1):8–12

    CAS  PubMed  Article  Google Scholar 

  • Ozer J et al (2008) The current state of serum biomarkers of hepatotoxicity. Toxicology 245(3):194–205

    CAS  PubMed  Article  Google Scholar 

  • Ørom UA, Nielsen FC, Lund AH (2008) MicroRNA-10a binds the 5′UTR of ribosomal protein mRNAs and enhances their translation. Mol Cell 30(4):460–471

    PubMed  Article  CAS  Google Scholar 

  • Pan C et al (2012) Down-regulation of MiR-127 facilitates hepatocyte proliferation during rat liver regeneration. PLoS One 7(6):1–10

    Article  CAS  Google Scholar 

  • Pastar I et al (2012) Induction of specific microRNAs inhibits cutaneous wound healing. J Biol Chem 287(35):29324–29335

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • Pavkovic M, Riefke B, Ellinger-Ziegelbauer H (2014) Urinary microRNA profiling for identification of biomarkers after cisplatin-induced kidney injury. Toxicology 324:147–157

    CAS  PubMed  Article  Google Scholar 

  • Pavkovic M, Vaidya VS (2016) MicroRNAs and drug-induced kidney injury. Pharmacol Ther 163:48–57

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • Pellegrini KL et al (2014) MicroRNA-155 deficient mice experience heightened kidney toxicity when dosed with cisplatin. Toxicol Sci 141(2):484–492

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • Pellegrini KL et al (2015) Application of small RNA sequencing to identify microRNAs in acute kidney injury and fibrosis. Toxicol Appl Pharmacol 312:42–52

    PubMed  Article  CAS  Google Scholar 

  • Porrello ER et al (2011a) Transient regenerative potential of the neonatal mouse heart. Sci (New York, N.Y.) 331(6020):1078–1080

    CAS  Article  Google Scholar 

  • Porrello ER, Johnson BA, Aurora AB (2011b) MiR-15 family regulates postnatal mitotic arrest of cardiomyocytes. Circulation 109(6):670–679

    CAS  Article  Google Scholar 

  • Porrello ER et al (2013) Regulation of neonatal and adult mammalian heart regeneration by the miR-15 family. Proc Natl Acad Sci USA 110(1):187–192

    CAS  PubMed  Article  Google Scholar 

  • Poss KD, Wilson LG, Keating MT (2002) Heart regeneration in zebrafish. Science 298(5601):2188–2190

    CAS  PubMed  Article  Google Scholar 

  • Qureshi ZP et al (2011) Market withdrawal of new molecular entities approved in the United States from 1980 to 2009. Pharmacoepidemiol Drug Saf 20(7):772–777

    PubMed  Article  Google Scholar 

  • Ramachandran K et al (2013) Human miRNome profiling identifies microRNAs differentially present in the urine after kidney injury. Clin Chem 59(12):1742–1752

    CAS  PubMed  Article  Google Scholar 

  • Rewa O, Bagshaw SM (2014) Acute kidney injury-epidemiology, outcomes and economics. Nat Revi Nephrol 10(4):193–207

    CAS  Article  Google Scholar 

  • Rodrigues PM et al (2015) Inhibition of NF-κB by deoxycholic acid induces miR-21/PDCD4-dependent hepatocellular apoptosis. Sci Rep 5(17528):1–17

    Google Scholar 

  • Roy S et al (2016) Down-regulation of miR-192-5p protects from oxidative stress-induced acute liver injury. Clin Sci (London, England: 1979 130(14):1197–1207

  • Ruby JG, Jan CH, Bartel DP (2007) Intronic microRNA precursors that bypass Drosha processing. Nature 448(7149):83–86

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • Saikumar J et al (2012) Expression, circulation, and excretion profile of microRNA-21,-155, and-18a following acute kidney injury. Toxicol Sci 129(2):256–267

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • Saikumar J, Ramachandran K, Vaidya VS (2014) Noninvasive micromarkers. Clin Chem 60(9):1158–1173

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • Saxena A, Tabin CJ (2010) miRNA-processing enzyme Dicer is necessary for cardiac outflow tract alignment and chamber septation. Proc Natl Acad Sci 107(1):87–91

    CAS  PubMed  Article  Google Scholar 

  • Sekine S et al (2009a) Disruption of Dicer1 induces dysregulated fetal gene expression and promotes hepatocarcinogenesis. Gastroenterology 136(7):2304–2315

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • Sekine S et al (2009b) Dicer is required for proper liver zonation. J Pathol 219(3):365–372

    CAS  PubMed  Article  Google Scholar 

  • Seok J-KK et al (2014) MicroRNA-382 induced by HIF-1α is an angiogenic miR targeting the tumor suppressor phosphatase and tensin homolog. Nucl Acids Res 42(12):8062–8072

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • Sequeira-Lopez MS et al (2010) The MicroRNA-processing enzyme dicer maintains juxtaglomerular cells. J Am Soc Nephrol 21(3):460–467

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • Sharma AD et al (2011) MicroRNA-221 regulates FAS-induced fulminant liver failure. Hepatology (Baltimore, Md.) 53(5):1651–1661

  • Song G et al (2010) MicroRNAs control hepatocyte proliferation during liver regeneration. Hepatology 51(5):1735–1743

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • Starkey Lewis PJ et al. (2011) Circulating microRNAs as potential markers of human drug-induced liver injury. Hepatology (Baltimore, Md.) 54(5):1767–1776

  • Su H et al (2009) Essential and overlapping functions for mammalian Argonautes in microRNA silencing. Genes Dev 23(3):304–317

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • Sun L et al (2016) miR-23b improves cognitive impairments in traumatic brain injury by targeting ATG12-mediated neuronal autophagy. Behav Brain Res. doi:10.1016/j.bbr.2016.09.020

  • Susantitaphong P et al (2013) World incidence of AKI: a meta-analysis. Clin J Am Soc Nephrol CJASN 8(9):1482–1493

    PubMed  Article  Google Scholar 

  • Tang R et al (2012) Mouse miRNA-709 directly regulates miRNA-15a/16-1 biogenesis at the posttranscriptional level in the nucleus: evidence for a microRNA hierarchy system. Cell Res 22(3):504–515

    CAS  PubMed  Article  Google Scholar 

  • Tony H, Yu K, Qiutang Z (2015) MicroRNA-208a silencing attenuates doxorubicin induced myocyte apoptosis and cardiac dysfunction. Oxid Med Cell Longev 2015:1–6

    Article  CAS  Google Scholar 

  • Tsai W-CC et al (2012) MicroRNA-122 plays a critical role in liver homeostasis and hepatocarcinogenesis. J Clin Investig 122(8):2884–2897

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • van Rooij E et al (2009) A family of microRNAs encoded by myosin genes governs myosin expression and muscle performance. Dev Cell 17(5):662–673

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  • van Rooij E, Purcell AL, Levin AA (2012) Developing microRNA therapeutics. Circ Res 110(3):496–507

    PubMed  Article  CAS  Google Scholar 

  • Vaidya VS et al (2010) Kidney injury molecule-1 outperforms traditional biomarkers of kidney injury in preclinical biomarker qualification studies. Nat Biotechnol 28(5):478–485

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • Vaporidi K, Vergadi E, Kaniaris E, Hatziapostolou M, Lagoudaki E, Georgopoulos D, Zapol WM, Bloch KD, Iliopoulos D (2012) Pulmonary microRNA profiling in a mouse model of ventilator-induced lung injury. Am J Physiol Lung Cell Mol Physiol 303(3):L199–L207

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • Waikar SS et al (2012) Imperfect gold standards for kidney injury biomarker evaluation. J Am Soc Nephrol JASN 23(1):13–21

    CAS  PubMed  Article  Google Scholar 

  • Wang K et al (2009) Circulating microRNAs, potential biomarkers for drug-induced liver injury. Proc Natl Acad Sci USA 106(11):4402–4407

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • Wang G-KK et al (2010a) Circulating microRNA: a novel potential biomarker for early diagnosis of acute myocardial infarction in humans. Eur Heart J 31(6):659–666

    PubMed  Article  CAS  Google Scholar 

  • Wang J et al (2010b) Bmp signaling regulates myocardial differentiation from cardiac progenitors through a MicroRNA-mediated mechanism. Dev Cell 19(6):903–912

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • Wang J et al (2010c) TransmiR: a transcription factor-microRNA regulation database. Nucl Acids Res 38(Database issue):D119–D122

  • Wang H et al (2015) Recent progress in microRNA delivery for cancer therapy by non-viral synthetic vectors. Adv Drug Deliv Rev 81:142–160

    CAS  PubMed  Article  Google Scholar 

  • Ward J et al (2014) Circulating microRNA profiles in human patients with acetaminophen hepatotoxicity or ischemic hepatitis. Proc Natl Acad Sci USA 111(33):12169–12174

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • Wei Q et al (2010) Targeted deletion of Dicer from proximal tubules protects against renal ischemia-reperfusion injury. J Am Soc Nephrol JASN 21(5):756–761

    CAS  PubMed  Article  Google Scholar 

  • Wei Y et al (2014) Importin 8 regulates the transport of mature MicroRNAs into the cell nucleus. J Biol Chem 289(15):10270–10275

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • Wei Q et al (2016) MicroRNA-489 induction by hypoxia-inducible factor-1 protects against ischemic kidney injury. J Am Soc Nephrol JASN 27:2784–2796

    PubMed  Google Scholar 

  • Xie T et al (2012) MicroRNA-127 inhibits lung inflammation by targeting IgG Fcγ receptor I. J Immunol (Baltimore, Md.: 1950) 188(5):2437–2444

  • Yamakuchi M, Ferlito M (2008) miR-34a repression of SIRT1 regulates apoptosis. Proc Natl Acad Sci 105(36):13421–13426

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • Yamaura Y et al (2012) Plasma microRNA profiles in rat models of hepatocellular injury, cholestasis, and steatosis. PLoS One 7(2):1–13

    Article  CAS  Google Scholar 

  • Yan-nan B et al (2014) MicroRNA-21 accelerates hepatocyte proliferation in vitro via PI3 K/Akt signaling by targeting PTEN. Biochem Biophys Res Commun 443(3):802–807

    PubMed  Article  CAS  Google Scholar 

  • Yang D et al (2016) MicroRNA-125b-5p mimic inhibits acute liver failure. Nat Commun 7(11916):1–11

    Google Scholar 

  • Yin K-JJ et al (2010) miR-497 regulates neuronal death in mouse brain after transient focal cerebral ischemia. Neurobiol Dis 38(1):17–26

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • Yoshioka W, Higashiyama W, Tohyama C (2011) Involvement of microRNAs in dioxin-induced liver damage in the mouse. Toxicol Sci 122(2):457–465

    CAS  PubMed  Article  Google Scholar 

  • Yuan B et al (2011) Down-regulation of miR-23b may contribute to activation of the TGF-β1/Smad3 signalling pathway during the termination stage of liver regeneration. FEBS Lett 585(6):927–934

    CAS  PubMed  Article  Google Scholar 

  • Yuan Q et al (2013) MicroRNA-221 overexpression accelerates hepatocyte proliferation during liver regeneration. Hepatology (Baltimore, Md.) 57(1):299–310

  • Zeng Z et al (2013) Upregulation of miR-146a contributes to the suppression of inflammatory responses in LPS-induced acute lung injury. Exp Lung Res 39(7):275–282

    CAS  PubMed  Article  Google Scholar 

  • Zhao Y et al (2007) Dysregulation of cardiogenesis, cardiac conduction, and cell cycle in mice lacking miRNA-1-2. Cell 129(2):303–317

    CAS  PubMed  Article  Google Scholar 

  • Zhao Y, Samal E, Srivastava D (2005) Serum response factor regulates a muscle-specific microRNA that targets Hand2 during cardiogenesis. Nature 436(7048):214–220

    CAS  PubMed  Article  Google Scholar 

  • Zhong X et al (2013) miR-21 is a key therapeutic target for renal injury in a mouse model of type 2 diabetes. Diabetologia 56(3):663–674

    CAS  PubMed  Article  Google Scholar 

  • Zhou J et al (2012) Down-regulation of microRNA-26a promotes mouse hepatocyte proliferation during liver regeneration. PLoS one 7(4):1–7

    CAS  Google Scholar 

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Acknowledgements

We thank Dr. Mira Pavkovic and Dr. Mariana Cardenas-Gonzalez for invaluable suggestions during the write up of this review article. Work in the Vaidya laboratory was supported by Outstanding New Environmental Sciences (ONES) award from NIH/NIEHS (ES017543) and Innovation in Regulatory Science Award from Burroughs Wellcome Fund (BWF-1012518).

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Correspondence to Vishal S. Vaidya.

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Gerlach, C.V., Vaidya, V.S. MicroRNAs in injury and repair. Arch Toxicol 91, 2781–2797 (2017). https://doi.org/10.1007/s00204-017-1974-1

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  • DOI: https://doi.org/10.1007/s00204-017-1974-1

Keywords

  • MicroRNAs
  • Injury
  • Repair
  • Liver
  • Heart
  • Kidney