The Role of ADAR1 and ADAR2 in the Regulation of miRNA-21 in Idiopathic Pulmonary Fibrosis
Por:
Díaz-Piña G., Ordoñez-Razo R.M., Montes E., Páramo I., Becerril C., Salgado A., Santibañez-Salgado J.A., Maldonado M., Ruiz V.
Publicada:
1 ene 2018
Categoría:
Pulmonary and respiratory medicine
Resumen:
Introduction: microRNAs (miRNAs) are small non-coding 1RNAs that post-transcriptionally regulate gene expression. Recent evidence shows that adenosine deaminases that act on RNA (ADAR) can edit miRNAs. miRNAs are involved in the development of different diseases, such as idiopathic pulmonary fibrosis (IPF). In IPF, about 40% of the miRNAs are differentially expressed with respect to controls. Among these miRNAs, miRNA-21 has been found over-expressed in IPF and its targets are anti-fibrosing molecules such as PELI1 and SPRY2. The objective of this study is to determine the role of ADAR1 and 2 on the expression of miRNA-21 in human lung fibroblasts trough quantification of gene expression, protein levels, and overexpression of ADAR1 and 2. Methods: Six control and six fibrotic primary fibroblast cell cultures were used for RNA extraction, ADAR1, ADAR2, PELI1, SPRY2, miRNA-21, and pri-miRNA-21 expression was measured. Subsequently, two fibrotic fibroblast cultures were used for overexpression of ADAR1 and ADAR2, and they were stimulated with TGFß1. Real-time PCR and Western blot were performed. Results: ADAR1 is significantly downregulated in IPF fibroblasts; the overexpression of ADAR1 and ADAR2 reestablishes the expression levels of miRNA-21, PELI1, and SPRY2 in fibroblasts of patients with IPF. Conclusion: These changes in the processing of miRNAs have great value in pathology diagnosis, including lung diseases, and play an important role in the understanding of molecular mechanisms involved in the development of different pathologies, as well as representing new therapeutic targets. © 2018, Springer Science+Business Media, LLC, part of Springer Nature.
Filiaciones:
Díaz-Piña G.:
Departamento de Investigación en Fibrosis Pulmonar, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Calz. Tlalpan 4502, Col. Sección XVI, Mexico City, Mexico
Ordoñez-Razo R.M.:
Hospital de Pediatría, Centro Médico Siglo XXI, Instituto Mexicano del Seguro Social, Unidad de Investigación Médica en Genética Humana, Av. Cuauhtémoc 330, Col. Doctores, Mexico City, Mexico
Montes E.:
Clínica de Asma, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Calz. Tlalpan 4502, Col. Sección XVI, Mexico City, Mexico
Páramo I.:
Clínica de Asma, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Calz. Tlalpan 4502, Col. Sección XVI, Mexico City, Mexico
Becerril C.:
Departamento de Investigación en Fibrosis Pulmonar, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Calz. Tlalpan 4502, Col. Sección XVI, Mexico City, Mexico
Salgado A.:
Departamento de Investigación en Fibrosis Pulmonar, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Calz. Tlalpan 4502, Col. Sección XVI, Mexico City, Mexico
Santibañez-Salgado J.A.:
Departamento de Cirugía Experimental, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Calz. Tlalpan 4502, Col. Sección XVI, Mexico City, Mexico
Maldonado M.:
Departamento de Investigación en Fibrosis Pulmonar, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Calz. Tlalpan 4502, Col. Sección XVI, Mexico City, Mexico
Ruiz V.:
Departamento de Investigación en Fibrosis Pulmonar, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Calz. Tlalpan 4502, Col. Sección XVI, Mexico City, Mexico
Laboratorio de Biología Molecular, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Calz. Tlalpan 4502, Col. Sección XVI, Mexico City, Mexico
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