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Lung

, Volume 196, Issue 4, pp 393–400 | Cite as

The Role of ADAR1 and ADAR2 in the Regulation of miRNA-21 in Idiopathic Pulmonary Fibrosis

  • Gabriela Díaz-Piña
  • Rosa Ma. Ordoñez-Razo
  • Eduardo Montes
  • Ignacio Páramo
  • Carina Becerril
  • Alfonso Salgado
  • J. Alfredo Santibañez-Salgado
  • Mariel Maldonado
  • Victor Ruiz
INTERSTITIAL LUNG DISEASE
  • 222 Downloads

Abstract

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 TGFβ1. 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.

Keywords

ADAR edition miRNA-21 IPF miRNA processing 

Notes

Acknowledgements

Gabriela Díaz Piña is a doctoral student from Programa de Doctorado en Ciencias Biomédicas, Universidad Nacional Autónoma de México (UNAM) and received the fellowship 290146 from Consejo Nacional de Ciencia y Tecnología, México (CONACyT).

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Gabriela Díaz-Piña
    • 1
  • Rosa Ma. Ordoñez-Razo
    • 2
  • Eduardo Montes
    • 3
  • Ignacio Páramo
    • 3
  • Carina Becerril
    • 1
  • Alfonso Salgado
    • 1
  • J. Alfredo Santibañez-Salgado
    • 4
  • Mariel Maldonado
    • 1
  • Victor Ruiz
    • 1
    • 5
  1. 1.Departamento de Investigación en Fibrosis PulmonarInstituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”Mexico CityMexico
  2. 2.Hospital de Pediatría, Centro Médico Siglo XXI, Instituto Mexicano del Seguro Social, Unidad de Investigación Médica en Genética HumanaMexico CityMexico
  3. 3.Clínica de AsmaInstituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”Mexico CityMexico
  4. 4.Departamento de Cirugía ExperimentalInstituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”Mexico CityMexico
  5. 5.Laboratorio de Biología MolecularInstituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”Mexico CityMexico

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