miRNA expresados diferencialmente en el plasma de pacientes con Nefritis Lupica clase II
dc.contributor.author | Martínez Olivares, Lilibeth | |
dc.date.accessioned | 2019-02-01T22:18:53Z | |
dc.date.available | 2019-02-01T22:18:53Z | |
dc.date.issued | 2019 | |
dc.description.abstract | Las enfermedades renales son un importante grupo de enfermedades de alto costo en Colombia. La importancia de estas enfermedades renales reside en que la alteración de las múltiples funciones del riñón, tareas que son en su mayoría vitales para el organismo, tiene consecuencias que podrían ser fatales sin la adecuada y pronta intervención. Por tanto, la identificación de biomarcadores que permitan un rápido y seguro diagnóstico en enfermedades tales como la nefritis lúpica, son de gran prioridad en el momento actual. En el presente trabajo, se describen perfiles de expresión diferencial de micro RNA en pacientes con nefritis lúpica clase II comparados con individuos sanos, como exploración inicial en la búsqueda de biomarcadores moleculares del daño renal en pacientes con lupus eritematoso sistémico. El objetivo de esta investigación es Identificar grupos de microRNAs expresados de forma diferencial en pacientes con nefritis lúpica clase II comparados con pacientes lupus sin nefritis e individuos sanos, los cuales podrían ser usados como biomarcadores específicos de esta clase de nefritis lúpica. Este trabajo se articula en el marco de un proyecto en el que se evalúan las demás clases de nefritis lúpica. Se tomó en cuenta todo paciente con diagnóstico de lupus eritematoso sistémico, vistos en el departamento de nefrología o reumatología en un centro asistencial en la ciudad de Barranquilla en edades de 15 a 40 años en el periodo comprendido del 10 de Enero 2014 al 10 de Enero 2015. Se secuenciaron 4 muestras de pacientes con nefritis lúpica clase II, 11 pacientes con lupus sin nefritis y 9 controles. Se obtuvo 10 ml de sangre venosa de cada uno ellos, se extrajo el RNA total del plasma, luego este ARN fue secuenciado en la plataforma Ilumina. Las secuencias obtenidas se compararon con las bases de datos miRBase y Ensembl. El análisis diferencial de expresión génica se llevó a cabo con edgeR y el análisis funcional se realizó con DIANA-miRPath. Se utilizó como variables de selección Fold-Change (≥ 2 o ≤ -2) y False-Discovery-Rate (≤ 0.05). Se identificaron 24 microRNAs circulantes con abundancia diferente al comparar LN clase II con los controles, de estos microRNAs trece, se describen por primera vez asociados a nefritis lúpica. Estos cambios en la abundancia de miARN, implican alteraciones en la red reguladora de miRNAs-mRNA en la patogénesis de LN que precede al inicio clínico de la enfermedad. Los resultados contribuyen así a la comprensión del proceso de la enfermedad, así como también permiten la identificación de biomarcadores específicos de la LN clase II que podrían ser detectados mediante métodos no invasivos como alternativa a la biopsia renal, disminuyendo así los riesgos asociados al diagnóstico de esta enfermedad. | spa |
dc.description.abstract | Kidney diseases are an important group of high-cost diseases in Colombia. The importance of these kidney diseases lies in the multifunctional functions of the kidney, which are vital for the body. Differential micro RNA expression profiles are described in patients with class II lupus nephritis compared to healthy individuals, as initial exploration in the search for molecular biomarkers of renal damage in patients with systemic lupus erythematosus. The aim of this research is to identify groups of differentially expressed microRNAs in patients with class II lupus nephritis compared to lupus patients without nephritis and healthy individuals, who could be used as specific biomarkers of this class of lupus nephritis. This work is articulated in the framework of a project in which the other classes of lupus nephritis are evaluated. All patients with a diagnosis of systemic lupus erythematosus, seen in the department of nephrology or rheumatology in a care center in the city of Barranquilla between the ages of 15 and 40 in the period from January 10, 2014 to January 10 2015. Four samples of patients with class II lupus nephritis were sequenced, 11 patients with lupus without nephritis and 9 controls. 10 ml of venous blood was obtained from each of them, the total RNA was extracted from the plasma, then this RNA was sequenced on the Ilumina platform. The sequences obtained were compared with the miRBase and Ensembl databases. Differential gene expression analysis was performed with edgeR and functional analysis was performed using DIANA-miRPath. Fold-Change (≥ 2 or ≤ -2) and False-Discovery-Rate (≤ 0.05) were used as selection variables. We identified 24 circulating microRNAs with different abundance when comparing LN class II controls, of these thirteen microRNAs, are first described associated with lupus nephritis. These changes in the abundance of miRNA involve alterations in the regulatory network of miRNAs-mRNA in the pathogenesis of LN that precedes the clinical onset of the disease. The results thus contribute to the understanding of the disease process, as well as the identification of specific biomarkers of LN class IV that could be detected by non-invasive methods as an alternative to renal biopsy, thus reducing the risks associated with the diagnosis of this sickness. | eng |
dc.identifier.uri | http://hdl.handle.net/20.500.12442/2551 | |
dc.language.iso | spa | spa |
dc.publisher | Ediciones Universidad Simón Bolívar | spa |
dc.publisher | Facultad de Ciencias Básicas y Biomédicas | spa |
dc.rights.accessrights | info:eu-repo/semantics/restrictedAccess | |
dc.rights.license | Licencia de Creative Commons Reconocimiento-NoComercial-CompartirIgual 4.0 Internacional | spa |
dc.subject | Nefritis lúpica clase II | spa |
dc.subject | Microrna | spa |
dc.subject | Lupus eritematoso sistémico | spa |
dc.subject | Biomarcadores | spa |
dc.subject | Class II lupic nephritis | eng |
dc.subject | Microrna | eng |
dc.subject | Systemic lupus erythematosus | eng |
dc.subject | Biomarkers | eng |
dc.title | miRNA expresados diferencialmente en el plasma de pacientes con Nefritis Lupica clase II | spa |
dc.type | Other | spa |
dcterms.references | Acuña, María José, et al. "Restoration of muscle strength in dystrophic muscle by angiotensin-1-7 through inhibition of TGF-β signalling." Human molecular genetics 23.5 (2013); Vol.2: Pág. 1237-1249. | eng |
dcterms.references | Enríquez Mejía, M. G. "Fisiopatología del lupus eritematoso sistémico." (2013); Vol. 1. Pág. 45-46. | spa |
dcterms.references | Cerrada, Mariela, et al. "Multi-stage feature selection by using genetic algorithms for fault diagnosis in gearboxes based on vibration signal." Sensors 15.9 (2015); Vol. 3: Pág. 23903-23926. | eng |
dcterms.references | Adams, Brian D., Henry Furneaux, and Bruce A. White. "The micro-ribonucleic acid (miRNA) miR-206 targets the human estrogen receptor-α (ERα) and represses ERα messenger RNA and protein expression in breast cancer cell lines." Molecular endocrinology 21.5 (2007); Vol. 1: Pág. 1132-1147. | eng |
dcterms.references | Illei, Gabor G., et al. "Biomarkers in systemic lupus erythematosus: II. Markers of disease activity." Arthritis & Rheumatology 50.7 (2004); Vol. 2: Pág. 2048-2065. | eng |
dcterms.references | Illei, Gabor G., et al. "Biomarkers in systemic lupus erythematosus: I. General overview of biomarkers and their applicability." Arthritis & Rheumatology 50.6 (2004); Vol. 1: Pág. 1709-1720. | eng |
dcterms.references | Esdaile, J. M., et al. "Routine immunologic tests in systemic lupus erythematosus: is there a need for more studies?." The Journal of rheumatology 23.11 (1996); Vol. 1: Pág. 1891-1896. | eng |
dcterms.references | Reyes-Thomas, Joyce, Irene Blanco, and Chaim Putterman. "Urinary biomarkers in lupus nephritis." Clinical reviews in allergy & immunology 40.3 (2011); Vol. 2: Pág. 138-150. | eng |
dcterms.references | Filipowicz, Witold, Suvendra N. Bhattacharyya, and Nahum Sonenberg. "Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight?." Nature reviews. Genetics 9.2 (2008); Vol. 2: Pág. 102. | eng |
dcterms.references | Cai, Yimei, et al. "A brief review on the mechanisms of miRNA regulation." Genomics, proteomics & bioinformatics 7.4 (2009): Vol. 1: Pág. 147-154. | eng |
dcterms.references | Calin, George Adrian, et al. "Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers." Proceedings of the National academy of Sciences of the United States of America 101.9 (2004): Vol. 2: Pág. 2999-3004. | eng |
dcterms.references | Kozomara, Ana, and Sam Griffiths-Jones. "miRBase: annotating high confidence microRNAs using deep sequencing data." Nucleic acids research 42.D1 (2013); Pág. D68-D73. | eng |
dcterms.references | Espinosa, Carlos E. Stahlhut, and Frank J. Slack. "Cancer Issue: The Role of MicroRNAs in Cancer." The Yale journal of biology and medicine 79.3-4 (2006); Pág. 131. | eng |
dcterms.references | Li, Chunsheng, et al. "Therapeutic microRNA strategies in human cancer." The AAPS journal 11.4 (2009): Pág. 747. | eng |
dcterms.references | Sección de Reumatología, Hospital Universitario San Vicente de Paul, Universidad de Antioquia. (2012): Medellín, Colombia. | spa |
dcterms.references | Ward, Michael M., et al. "Short‐term prediction of mortality in patients with systemic lupus erythematosus: Classification of outcomes using random forests." Arthritis Care & Research: Official Journal of the American College of Rheumatology 55.1 (2006): 74-80. | eng |
dcterms.references | Ahmadpoor, P., Dalili, N. & Rostami, M. An Update on Pathogenesis of Systemic Lupus Erythematosus. International Journal of Kidney Diseases, 8(3), (2014) 171-184. http://doi.org/24878938 | eng |
dcterms.references | González, L., et al. "Nefropatía lúpica. Presentación clínica, clasificación y tratamiento." Rev Colomb Reumatol 13 (2006): 307-33. | spa |
dcterms.references | Estes, Dorothy, and Charles L. Christian. "The natural history of systemic lupus erythematosus by prospective analysis." Medicine 50.2 (1971); Pág. 85-96. | eng |
dcterms.references | Harvey, A. McGehee, et al. "Systemic lupus erythematosus: review of the literature and clinical analysis of 138 cases." Medicine 33.4 (1954); Pág. 291. | eng |
dcterms.references | Cairns SA, Acheson EJ, Corbett CL, et al. The delayed appearance of an antinuclear facto and the diagnosis of systemic lupus erythematosus in glomerulonephritis. (1979); Vol. 55: Pág. 723-727. | eng |
dcterms.references | Egido De los Ríos, J. & Ortiz Arduán, A. Nefropatías glomerulares. In L. Hernando Avendaño, P. Aljama García, M. Arias Rodríguez, C. Caramelo Díaz (†), J. Egido De los Ríos & S. Peláez Lamas (Eds.), Nefrología Clínica (2003). (4ta ed., pp. 302-308). Madrid, España: Editorial Panamericana. | spa |
dcterms.references | Ruiz-Irastorza, G., Espinosa, G., Jiménez-Alonso, J., Pallarés, L. & Robles, A. Diagnóstico y tratamiento de la nefritis lúpica: El camino del consenso. Revista Clínica Española, 2012(3), 155-156. http://doi. org/10.1016/j.rce.2012.02.001. | spa |
dcterms.references | Pistiner, Moshe, et al. "Lupus erythematosus in the 1980s: a survey of 570 patients." Seminars in arthritis and rheumatism. (1991); Vol. 21. No. 1. | eng |
dcterms.references | Dai, Yong, et al. "Comprehensive analysis of microRNA expression patterns in renal biopsies of lupus nephritis patients." Rheumatology international 29.7 (2009): 749-754. | eng |
dcterms.references | Kobayashi, Hisato, et al. "High-resolution DNA methylome analysis of primordial germ cells identifies gender-specific reprogramming in mice." Genome research 23.4 (2013): 616-627. | eng |
dcterms.references | Papagregoriou, Gregory, et al. "A miR-1207-5p binding site polymorphism abolishes regulation of HBEGF and is associated with disease severity in CFHR5 nephropathy." PLoS One 7.2 (2012): e31021. | eng |
dcterms.references | Te, Jeannie L., et al. "Identification of unique microRNA signature associated with lupus nephritis." PloS one 5.5 (2010): e10344. | eng |
dcterms.references | White, N. M. A., et al. "miRNA profiling in metastatic renal cell carcinoma reveals a tumour-suppressor effect for miR-215." British journal of cancer 105.11 (2011): 1741-1749. | eng |
dcterms.references | Dimmeler, Stefanie, and Pierluigi Nicotera. "MicroRNAs in age‐related diseases." EMBO molecular medicine 5.2 (2013): 180-190. | eng |
dcterms.references | Vlachos, Ioannis S., et al. "DIANA-miRPath v3. 0: deciphering microRNA function with experimental support." Nucleic acids research 43.W1 (2015): W460-W466. | eng |
dcterms.references | Wang, Jinjun, et al. "Locality-constrained linear coding for image classification." Computer Vision and Pattern Recognition (CVPR), 2010 IEEE Conference on. IEEE, 2010. | eng |
dcterms.references | Lu, Ming, et al. "An analysis of human microRNA and disease associations." PloS one 3.10 (2008): e3420. | eng |
dcterms.references | Hsu, Justin Bo-Kai, et al. "miRTar: an integrated system for identifying miRNA-target interactions in human." BMC bioinformatics 12.1 (2011): 300. | eng |
dcterms.references | Dong, Bin, and Shuangying Jiang. "Characteristics and behaviors of soluble microbial products in sequencing batch membrane bioreactors at various sludge retention times." Desalination 243.1-3 (2009): 240-250. | eng |
dcterms.references | Ruepp, Andreas, et al. "PhenomiR: a knowledgebase for microRNA expression in diseases and biological processes." Genome biology 11.1 (2010): R6. | eng |
dcterms.references | Shivaprasad, Padubidri V., et al. "A microRNA superfamily regulates nucleotide binding site–leucine-rich repeats and other mRNAs." The Plant Cell 24.3 (2012): 859-874. | eng |
dcterms.references | Jostins, Luke, et al. "Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease." Nature491.7422 (2012): 119-124. | eng |
dcterms.references | Kyttaris, Vasileios C., et al. "Calcium signaling in systemic lupus erythematosus T cells: a treatment target." Arthritis & Rheumatology 63.7 (2011): 2058-2066. | eng |
dcterms.references | Chang, Cui-Zu, et al. "Experimental observation of the quantum anomalous Hall effect in a magnetic topological insulator." Science 340.6129 (2013): 167-170. | eng |
dcterms.references | Sabourin, L. A., et al. "Caspase 3 cleavage of 557 the Ste20-related kinase SLK releases and activates an apoptosis-inducing kinase domain 558 and an actin-disassembling region." Mol Cell Biol 20.684-696 (2000): 559. | eng |
dcterms.references | Min, Yuanzeng, et al. "Clinical translation of nanomedicine." Chemical reviews 115.19 (2015): 11147-11190. | eng |
dcterms.references | Lee, Yoontae, et al. "MicroRNA maturation: stepwise processing and subcellular localization." The EMBO journal 21.17 (2002): 4663-4670. | eng |
dcterms.references | Sabourin, Luc A., and Michael A. Rudnicki. "The molecular regulation of myogenesis." Clinical genetics 57.1 (2000): 16-25. | eng |
dcterms.references | Skalsky, Rebecca L., et al. "The viral and cellular microRNA targetome in lymphoblastoid cell lines." PLoS pathogens 8.1 (2012): e1002484. | eng |
dcterms.references | AlFadhli, Suad, Aqeel AM Ghanem, and Rasheeba Nizam. "Genome‐wide differential expression reveals candidate genes involved in the pathogenesis of lupus and lupus nephritis." International journal of rheumatic diseases 19.1 (2016): 55-64. | eng |
dcterms.references | Chang, Shih-Chung, et al. "The ER aminopeptidase, ERAP1, trims precursors to lengths of MHC class I peptides by a “molecular ruler” mechanism." Proceedings of the National Academy of Sciences of the United States of America 102.47 (2005): 17107-17112. | eng |
dcterms.references | Gottwein, Eva, et al. "Viral microRNA targetome of KSHV-infected primary effusion lymphoma cell lines." Cell host & microbe 10.5 (2011): 515-526. | eng |
dcterms.references | Zhang, Xiaorong, et al. "MicroRNA directly enhances mitochondrial translation during muscle differentiation." Cell158.3 (2014): 607-619. | eng |
dcterms.references | Karginov, Fedor V., and Gregory J. Hannon. "Remodeling of Ago2–mRNA interactions upon cellular stress reflects miRNA complementarity and correlates with altered translation rates." Genes & development 27.14 (2013): 1624-1632. | eng |
dcterms.references | Spada, Cristiano, et al. "Colon capsule versus CT colonography in patients with incomplete colonoscopy: a prospective, comparative trial." Gut 64.2 (2015): 272-281. | eng |
dcterms.references | Edwards, Lindsay J., Masayuki Mizui, and Vasileios Kyttaris. "Signal transducer and activator of transcription (STAT) 3 inhibition delays the onset of lupus nephritis in MRL/lpr mice." Clinical Immunology 158.2 (2015): 221-230. | eng |
dcterms.references | Su, Zhenqiang, et al. "A comprehensive assessment of RNA-seq accuracy, reproducibility and information content by the Sequencing Quality Control Consortium." Nature biotechnology32.9 (2014): 903. | eng |
dcterms.references | Pillai RS, Bhattacharyya SN, Artus CG, Zoller T, Cougot N, Basyuk E, Bertrand E,Filipowicz W. Inhibition of translational initiation by Let-7 MicroRNA in human cells. (2009) Science 309: 1573–1576. | eng |
dcterms.references | Sheedy, Frederick J., et al. "Negative regulation of TLR4 via targeting of the proinflammatory tumor suppressor PDCD4 by the microRNA miR-21." Nature immunology 11.2 (2010): 141-147. | eng |
dcterms.references | Hilliard A, Hilliard B, Zheng S-J, Sun H, Miwa T, Song W et al. (2006). Translational regulation of autoimmune inflammation and lymphoma genesis by programmed cell death 4. J Immunol 177: 8095–8102. | eng |
dcterms.references | Garchow, Barry G., et al. "Silencing of microRNA‐21 in vivo ameliorates autoimmune splenomegaly in lupus mice." EMBO molecular medicine 3.10 (2011): 605-615. | eng |
dcterms.references | Hom, Geoffrey, et al. "Association of systemic lupus erythematosus with C8orf13–BLK and ITGAM–ITGAX." New England Journal of Medicine 358.9 (2008): 900-909. | eng |
dcterms.references | Kim, Min-Sik, et al. "A draft map of the human proteome." Nature509.7502 (2014): 575-581. | eng |
dcterms.references | Ward, Elizabeth, et al. "Childhood and adolescent cancer statistics, 2014." CA: a cancer journal for clinicians 64.2 (2014): 83-103. | eng |
dcterms.references | Lagier-Tourenne, Clotilde, et al. "ADCK3, an ancestral kinase, is mutated in a form of recessive ataxia associated with coenzyme Q 10 deficiency." The American Journal of Human Genetics 82.3 (2008): 661-672. | eng |
dcterms.references | Reddy, Vemuri B., y col. "La catepsina S provoca picor y señales a través de receptores activados por proteasa". The Journal of investigative dermatology 130.5 (2010): 1468. | eng |
dcterms.references | Schaeffer, Valerie, et al. "Reductions in laminin β2 mRNA translation are responsible for impaired IGFBP-5-mediated mesangial cell migration in the presence of high glucose." American Journal of Physiology-Renal Physiology 298.2 (2010): F314-F322. | eng |
dcterms.references | Ansieau, Stéphane, y col. "Inducción de EMT por las proteínas de torsión como un efecto colateral de la inactivación de la senescencia prematura que promueve el tumor". Cancer cell 14.1 (2008): 79-89. | spa |
dcterms.references | Kameswaran, Vasumathi, et al. "Epigenetic regulation of the DLK1-MEG3 microRNA cluster in human type 2 diabetic islets." Cell metabolism 19.1 (2014): 135-145. | eng |
dcterms.references | Helwak, Aleksandra, et al. "Mapping the human miRNA interactome by CLASH reveals frequent noncanonical binding." Cell 153.3 (2013): 654-665. | eng |
dcterms.references | Whisnant, Adam W., et al. "In-depth analysis of the interaction of HIV-1 with cellular microRNA biogenesis and effector mechanisms." MBio 4.2 (2013): e00193-13. | eng |
dcterms.references | Kundaje, Anshul, et al. "Integrative analysis of 111 reference human epigenomes." Nature 518.7539 (2015): 317-330. | eng |
dcterms.references | Palm, Rainer, Dimiter Driankov, and Hans Hellendoorn. Model based fuzzy control: fuzzy gain schedulers and sliding mode fuzzy controllers. Springer Science & Business Media, 2013. | eng |
dcterms.references | Hedrich, Christian M., Jose C. Crispin, and George C. Tsokos. "Epigenetic regulation of cytokine expression in systemic lupus erythematosus with special focus on T cells." Autoimmunity 47.4 (2014): 234-241. | eng |
sb.programa | Maestría en Genética | spa |
sb.sede | Sede Barranquilla | spa |