Información de la revista
Vol. 33. Núm. 6.noviembre 2013
Páginas 751-868
Vol. 33. Núm. 6.noviembre 2013
Páginas 751-868
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Los microARN en el riñón: nuevos biomarcadores de la lesión renal aguda
microRNAs in the kidney: Novel biomarkers of Acute Kidney Injury
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16052
Elia Aguado-Frailea, Edurne Ramosa, Elisa Condea, Macarena Rodrígueza, Fernando Liañob, M. Laura García-Bermejoa
a Patología de Sistemas y Cáncer, Hospital Universitario Ramón y Cajal. Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid,
b Servicio de Nefrología, Hospital Universitario Ramón y Cajal. Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid,
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Los microARN son pequeñas moléculas endógenas de ARN de vital importancia para la regulación de la expresión génica. Se han convertido en los mediadores biológicos más importantes que se han caracterizado en los últimos diez años. Participan en casi todos los procesos celulares, por lo que su desregulación está asociada al desarrollo de muchas patologías, entre las que se encuentran las renales. Existen cada vez más pruebas que demuestran que los microARN son reguladores claves de la función y el desarrollo renal, aunque también se encuentran en el origen de algunas enfermedades renales. Los estudios más recientes han concluido que estas moléculas pueden ser secretadas al exterior de la célula, lo que permite que puedan ser detectadas en fluidos periféricos como la orina y el suero. Además, los microARN circulantes detectados en los fluidos corporales pueden ser biomarcadores adecuados de las enfermedades renales, entre las que se incluye la lesión renal aguda. Esta nueva generación de biomarcadores renales podría tener consecuencias importantes para la práctica clínica, ya que podrían contribuir significativamente a la mejora del manejo de los pacientes. En este trabajo se revisa la implicación de los microARN en la homeostasis y la función renal y el papel de los microARN circulantes como nuevos biomarcadores de las enfermedades renales, centrándonos en su potencial utilidad para el manejo de la lesión renal aguda.

Palabras clave:
Biomarcadores
Palabras clave:
Insuficiencia renal aguda
Palabras clave:
microRNAs

microRNAs are small, endogenous RNA molecules which are critical for a new step in the regulation of the gene expression. They have become the most critical biological mediators characterized in the last ten years. microRNAs participate in almost every cellular process, therefore their deregulation is associated with the development of a wide range of pathologies, including kidney diseases. Increasing evidence demonstrates that microRNAs are key regulators of the normal kidney function and development, but they are also at the basis of several renal diseases. Recent works have established that these molecules can be secreted to extracellular environments, enabling their detection in peripheral body fluids such as urine and serum. Moreover, circulating miRNAs detected in body fluids turn into suitable biomarkers of kidney diseases, including acute kidney injury. This new generation of renal biomarkers could have a great impact in the clinical practice, significantly contributing to improve patient management. In this review, we discuss over the implication of microRNAs in normal kidney function and homeostasis as well as the role of circulating miRNAs as novel biomarkers of kidney diseases, focusing on their potential usefulness in acute kidney injury management.

Keywords:
Biomarkers
Keywords:
Acute kidney injury
Keywords:
microRNAs
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Bibliografía
[1]
Krol J, Loedige I, Filipowicz W. The widespread regulation of microRNA biogenesis, function and decay. Nat Rev Genet 2010;11(9):597-610. [Pubmed]
[2]
Kozomara A, Griffiths-Jones S. miRBase: integrating microRNA annotation and deep-sequencing data. Nucleic Acids Res 2011;39(Database issue):D152-7. [Pubmed]
[3]
Treiber T, Treiber N, Meister G. Regulation of microRNA biogenesis and function. Thromb Haemost 2012;107(4):605-10.
[4]
Huntzinger E, Izaurralde E. Gene silencing by microRNAs: contributions of translational repression and mRNA decay. Nat Rev Genet 2011;12(2):99-110. [Pubmed]
[5]
van Rooij E, Sutherland LB, Qi X, Richardson JA, Hill J, Olson EN. Control of stress-dependent cardiac growth and gene expression by a microRNA. Science 2007;316(5824):575-9. [Pubmed]
[6]
Gatfield D, Le Martelot G, Vejnar CE, Gerlach D, Schaad O, Fleury-Olela F, et al. Integration of microRNA miR-122 in hepatic circadian gene expression. Genes Dev 2009;23(11):1313-26. [Pubmed]
[7]
Krol J, Busskamp V, Markiewicz I, Stadler MB, Ribi S, Richter J, et al. Characterizing light-regulated retinal microRNAs reveals rapid turnover as a common property of neuronal microRNAs. Cell 2010;141(4):618-31. [Pubmed]
[8]
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. [Pubmed]
[9]
Sun Y, Koo S, White N, Peralta E, Esau C, Dean NM, et al. Development of a micro-array to detect human and mouse microRNAs and characterization of expression in human organs. Nucleic Acids Res 2004;32(22):e188. [Pubmed]
[10]
Baskerville S, Bartel DP. Microarray profiling of microRNAs reveals frequent coexpression with neighboring miRNAs and host genes. RNA 2005;11(3):241-7. [Pubmed]
[11]
Chandrasekaran K, Karolina DS, Sepramaniam S, Armugam A, Wintour EM, Bertram JF, et al. Role of microRNAs in kidney homeostasis and disease. Kidney Int 2012;81(7):617-27. [Pubmed]
[12]
Wessely O, Agrawal R, Tran U. MicroRNAs in kidney development: lessons from the frog. RNA Biol 2010;7(3):296-9. [Pubmed]
[13]
Ho J, Ng KH, Rosen S, Dostal A, Gregory RI, Kreidberg JA. Podocyte-specific loss of functional microRNAs leads to rapid glomerular and tubular injury. J Am Soc Nephrol 2008;19(11):2069-75. [Pubmed]
[14]
Bai XY, Ma Y, Ding R, Fu B, Shi S, Chen XM. miR-335 and miR-34a Promote renal senescence by suppressing mitochondrial antioxidative enzymes. J Am Soc Nephrol 2011;22(7):1252-61. [Pubmed]
[15]
Shi S, Yu L, Chiu C, Sun Y, Chen J, Khitrov G, et al. Podocyte-selective deletion of dicer induces proteinuria and glomerulosclerosis. J Am Soc Nephrol 2008;19(11):2159-69. [Pubmed]
[16]
Zhdanova O, Srivastava S, Di L, Li Z, Tchelebi L, Dworkin S, et al. The inducible deletion of Drosha and microRNAs in mature podocytes results in a collapsing glomerulopathy. Kidney Int 2011;80(7):719-30. [Pubmed]
[17]
Sequeira-Lopez ML, Weatherford ET, Borges GR, Monteagudo MC, Pentz ES, Harfe BD, et al. The microRNA processing enzyme dicer maintains juxtaglomerular cells. J Am Soc Nephrol 2010;21(3):460-7. [Pubmed]
[18]
Sepramaniam S, Armugam A, Lim KY, Karolina DS, Swaminathan P, Tan JR, et al. MicroRNA 320a functions as a novel endogenous modulator of aquaporins 1 and 4 as well as a potential therapeutic target in cerebral ischemia. J Biol Chem 2010;285(38):29223-30. [Pubmed]
[19]
Flynt AS, Thatcher EJ, Burkewitz K, Li N, Liu Y, Patton JG. miR-8 microRNAs regulate the response to osmotic stress in zebrafish embryos. J Cell Biol 2009;185(1):115-27. [Pubmed]
[20]
Kato M, Zhang J, Wang M, Lanting L, Yuan H, Rossi JJ, et al. 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 U S A 2007;104(9):3432-7. [Pubmed]
[21]
Krupa A, Jenkins R, Luo DD, Lewis A, Phillips A, Fraser D. Loss of MicroRNA-192 promotes fibrogenesis in diabetic nephropathy. J Am Soc Nephrol 2010;21(3):438-47. [Pubmed]
[22]
Pandey P, Qin S, Ho J, Zhou J, Kreidberg JA. Systems biology approach to identify transcriptome reprogramming and candidate microRNA targets during the progression of polycystic kidney disease. BMC Syst Biol 2011;5:56. [Pubmed]
[23]
Lee SO, Masyuk T, Splinter P, Banales JM, Masyuk A, Stroope A, et al. MicroRNA15a modulates expression of the cell-cycle regulator Cdc25A and affects hepatic cystogenesis in a rat model of polycystic kidney disease. J Clin Invest 2008;118(11):3714-24. [Pubmed]
[24]
Gottardo F, Liu CG, Ferracin M, Calin GA, Fassan M, Bassi P, et al. Micro-RNA profiling in kidney and bladder cancers. Urol Oncol 2007;25(5):387-92. [Pubmed]
[25]
Jung M, Mollenkopf HJ, Grimm C, Wagner I, Albrecht M, Waller T, et al. MicroRNA profiling of clear cell renal cell cancer identifies a robust signature to define renal malignancy. J Cell Mol Med 2009;13(9B):3918-28. [Pubmed]
[26]
Redova M, Svoboda M, Slaby O. MicroRNAs and their target gene networks in renal cell carcinoma. Biochem Biophys Res Commun 2011;405(2):153-6. [Pubmed]
[27]
Korpal M, Lee ES, Hu G, Kang Y. 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 2008;283(22):14910-4. [Pubmed]
[28]
Park SM, Gaur AB, Lengyel E, Peter ME. The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2. Genes Dev 2008;22(7):894-907. [Pubmed]
[29]
Xiong M, Jiang L, Zhou Y, Qiu W, Fang L, Tan R, et al. The miR-200 family regulates TGF-¿1-induced renal tubular epithelial to mesenchymal transition through Smad pathway by targeting ZEB1 and ZEB2 expression. Am J Physiol Renal Physiol 2012;302(3):F369-79. [Pubmed]
[30]
Wei Q, Bhatt K, He HZ, Mi QS, Haase VH, Dong Z. Targeted deletion of Dicer from proximal tubules protects against renal ischemia-reperfusion injury. J Am Soc Nephrol 2010;21(5):756-61. [Pubmed]
[31]
Godwin JG, Ge X, Stephan K, Jurisch A, Tullius SG, Iacomini J. Identification of a microRNA signature of renal ischemia reperfusion injury. Proc Natl Acad Sci U S A 2010;107(32):14339-44. [Pubmed]
[32]
Shapiro MD, Bagley J, Latz J, Godwin JG, Ge X, Tullius SG, et al. MicroRNA expression data reveals a signature of kidney damage following Ischemia Reperfusion Injury. PLoS One 2011;6(8):e23011. [Pubmed]
[33]
Aguado-Fraile E, Ramos E, Sáenz-Morales D, Conde E, Blanco-Sánchez I, Stamatakis K, et al. miR-127 protects proximal tubule cells against ischemia/reperfusion: identification of kinesin family member 3B as miR-127 target. PLoS One 2012;7(9):e44305. [Pubmed]
[34]
Liu F, Lou YL, Wu J, Ruan QF, Xie A, Guo F, et al. Upregulation of MicroRNA-210 regulates renal angiogenesis mediated by activation of VEGF signaling pathway under ischemia/perfusion injury in vivo and in vitro. Kidney Blood Press Res 2012;35(3):182-91. [Pubmed]
[35]
Cantaluppi V, Gatti S, Medica D, Figliolini F, Bruno S, et al. Microvesicles derived from endothelial progenitor cells protect the kidney from ischemia-reperfusion injury by microRNA-dependent reprogramming of resident renal cells. Kidney Int 2012;82(4):412-27. [Pubmed]
[36]
Février B, Raposo G. Exosomes: endosomal-derived vesicles shipping extracellular messages. Curr Opin Cell Biol 2004;16(4):415-21. [Pubmed]
[37]
Fleischhacker M, Schmidt B. Circulating nucleic acids (CNAs) and cancer--a survey. Biochim Biophys Acta 2007;1775(1):181-232. [Pubmed]
[38]
Reid G, Kirschner MB, van Zandwijk N. Circulating microRNAs: Association with disease and potential use as biomarkers. Crit Rev Oncol Hematol 2011;80(2):193-208. [Pubmed]
[39]
Chen X, Ba Y, Ma L, Cai X, Yin Y, Wang K, et al. Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res 2008;18(10):997-1006. [Pubmed]
[40]
Kosaka N, Iguchi H, Yoshioka Y, Takeshita F, Matsuki Y, Ochiya T. Secretory mechanisms and intercellular transfer of microRNAs in living cells. J Biol Chem 2010;285(23):17442-52. [Pubmed]
[41]
Hunter MP, Ismail N, Zhang X, Aguda BD, Lee EJ, Yu L, et al. Detection of microRNA expression in human peripheral blood microvesicles. PLoS One 2008;3(11):e3694. [Pubmed]
[42]
Gallo A, Tandon M, Alevizos I, Illei GG. The majority of microRNAs detectable in serum and saliva is concentrated in exosomes. PLoS One 2012;7(3):e30679. [Pubmed]
[43]
Arroyo JD, Chevillet JR, Kroh EM, Ruf IK, Pritchard CC, Gibson DF, et al. Argonaute2 complexes carry a population of circulating microRNAs independent of vesicles in human plasma. Proc Natl Acad Sci U S A 2011;108(12):5003-8. [Pubmed]
[44]
Lorenzen JM, Kielstein JT, Hafer C, Gupta SK, Kümpers P, Faulhaber-Walter R, et al. Circulating miR-210 predicts survival in critically ill patients with acute kidney injury. Clin J Am Soc Nephrol 2011;6(7):1540-6. [Pubmed]
[45]
Saikumar J, Hoffmann D, Kim TM, Ramirez V, Zhang Q, Goering PL, et al. Expression, circulation and excretion profile of microRNA-21, -155, and -18a following acute kidney injury. Toxicol Sci 2012;129(2):256-67. [Pubmed]
[46]
Lan YF, Chen HH, Lai PF, Cheng CF, Huang YT, Lee YC, et al. MicroRNA-494 reduces ATF3 expression and promotes AKI. J Am Soc Nephrol 2012;23(12):2012-23. [Pubmed]
[47]
Aguado-Fraile E, Ramos E, Conde E, Rodríguez M, Lietor A, Candela-Toha A, et al. A novel set of serum microRNAs could be useful biomarkers of Acute Kidney Injury. In preparation.
[48]
Pickering JW, Endre ZH. Secondary prevention of acute kidney injury. Curr Opin Crit Care 2009;15(6):488-97. [Pubmed]
[49]
Murugan R, Kellum JA. Acute kidney injury: what's the prognosis? Nat Rev Nephrol 2011;7(4):209-17. [Pubmed]
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