miRNA expresados diferencialmente en el plasma de pacientes con Nefritis Lupica clase II
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Fecha
2019
Autores
Martínez Olivares, Lilibeth
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Ediciones Universidad Simón Bolívar
Facultad de Ciencias Básicas y Biomédicas
Facultad de Ciencias Básicas y Biomédicas
Resumen
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.
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.
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.
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Palabras clave
Nefritis lúpica clase II, Microrna, Lupus eritematoso sistémico, Biomarcadores, Class II lupic nephritis, Microrna, Systemic lupus erythematosus, Biomarkers