ADAR1 Isoforms Regulate <i>Let-7d</i> Processing in Idiopathic Pulmonary Fibrosis
Double-stranded RNA adenosine deaminase 1 (ADAR1) is significantly down-regulated in fibroblasts derived from Idiopathic Pulmonary Fibrosis (IPF) patients, and its overexpression restored levels of <i>miRNA-21</i>, <i>PELI1</i>, and <i>SPRY2</i>. There are two ADA...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-08-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/23/16/9028 |
| _version_ | 1797432100010328064 |
|---|---|
| author | Gabriela Díaz-Piña Karla Rubio Rosa M. Ordoñez-Razo Guillermo Barreto Eduardo Montes Carina Becerril Alfonso Salgado Héctor Cabrera-Fuentes Arnoldo Aquino-Galvez Angeles Carlos-Reyes Victor Ruiz |
| author_facet | Gabriela Díaz-Piña Karla Rubio Rosa M. Ordoñez-Razo Guillermo Barreto Eduardo Montes Carina Becerril Alfonso Salgado Héctor Cabrera-Fuentes Arnoldo Aquino-Galvez Angeles Carlos-Reyes Victor Ruiz |
| author_sort | Gabriela Díaz-Piña |
| collection | DOAJ |
| description | Double-stranded RNA adenosine deaminase 1 (ADAR1) is significantly down-regulated in fibroblasts derived from Idiopathic Pulmonary Fibrosis (IPF) patients, and its overexpression restored levels of <i>miRNA-21</i>, <i>PELI1</i>, and <i>SPRY2</i>. There are two ADAR1 isoforms in humans, ADAR1-p110 and ADAR1-p150, generated by an alternative promoter. <i>Let-7d</i> is considered an essential microRNA in Pulmonary Fibrosis (PF). In silico analysis revealed <i>COL3A1</i> and <i>SMAD2</i>, proteins involved in the development of IPF, as <i>Let-7d</i> targets. We analyzed the role of ADAR1-p110 and ADAR1-p150 isoforms in the regulation of <i>Let-7d</i> maturation and the effect of this regulation on the expression of <i>COL3A1</i> and <i>SMAD2</i> in IPF fibroblast. We demonstrated that differential expression and subcellular distribution of ADAR1 isoforms in fibroblasts contribute to the up-regulation of <i>pri-miR-Let-7d</i> and down-regulation of mature <i>Let-7d</i>. Induction of overexpression of ADAR1 reestablishes the expression of <i>pri-miR-Let-7d</i> and <i>Let-7d</i> in lung fibroblasts. The reduction of mature <i>Let-7d</i> upregulates the expression of <i>COL3A1</i> and <i>SMAD2</i>. Thus, ADAR1 isoforms and <i>Let-7d</i> could have a synergistic role in IPF, which is a promising explanation in the mechanisms of fibrosis development, and the regulation of both molecules could be used as a therapeutic approach in IPF. |
| first_indexed | 2024-03-09T09:56:23Z |
| format | Article |
| id | doaj.art-70f5e3ed7193483e89bc7781a10a8e49 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T09:56:23Z |
| publishDate | 2022-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-70f5e3ed7193483e89bc7781a10a8e492023-12-01T23:47:11ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-08-012316902810.3390/ijms23169028ADAR1 Isoforms Regulate <i>Let-7d</i> Processing in Idiopathic Pulmonary FibrosisGabriela Díaz-Piña0Karla Rubio1Rosa M. Ordoñez-Razo2Guillermo Barreto3Eduardo Montes4Carina Becerril5Alfonso Salgado6Héctor Cabrera-Fuentes7Arnoldo Aquino-Galvez8Angeles Carlos-Reyes9Victor Ruiz10Molecular Biology Laboratory, Pulmonary Fibrosis Department, National Institute of Respiratory Diseases “Ismael Cosío Villegas”, Calzada de Tlalpan No. 4502, Col. Sección XVI, Mexico City 14080, MexicoUniversité de Lorraine, CNRS, Laboratoire IMoPA, UMR 7365, F-54000 Nancy, FranceMedical Research Unit in Human Genetics, Pediatric Hospital “Dr. Silvestre Frenk Freud”, National Medical Center “Siglo XXI”, Mexican Social Security Institute, Av. Cuauhtémoc No. 330, Col. Doctores, Delegación Cuauhtémoc, Mexico City 06720, MexicoUniversité de Lorraine, CNRS, Laboratoire IMoPA, UMR 7365, F-54000 Nancy, FranceMolecular Biology Laboratory, Pulmonary Fibrosis Department, National Institute of Respiratory Diseases “Ismael Cosío Villegas”, Calzada de Tlalpan No. 4502, Col. Sección XVI, Mexico City 14080, MexicoCellular Biology Laboratory, Pulmonary Fibrosis Department, National Institute of Respiratory Diseases “Ismael Cosío Villegas”, Calzada de Tlalpan No. 4502, Col. Sección XVI, Mexico City 14080, MexicoRheumatic Diseases Research Laboratory, Pulmonary Fibrosis Department, National Institute of Respiratory Diseases “Ismael Cosío Villegas”, Calzada de Tlalpan No. 4502, Col. Sección XVI, Mexico City 14080, MexicoMedical School, Institute of Biochemistry, Justus-Liebig-University, 35390 Giessen, GermanyMolecular Biology Laboratory, Pulmonary Fibrosis Department, National Institute of Respiratory Diseases “Ismael Cosío Villegas”, Calzada de Tlalpan No. 4502, Col. Sección XVI, Mexico City 14080, MexicoOnco-Immunobiology Laboratory, Department of Chronic-Degenerative Diseases, National Institute of Respiratory Diseases “Ismael Cosío Villegas”, Calzada de Tlalpan No. 4502, Col. Sección XVI, Mexico City 14080, MexicoMolecular Biology Laboratory, Pulmonary Fibrosis Department, National Institute of Respiratory Diseases “Ismael Cosío Villegas”, Calzada de Tlalpan No. 4502, Col. Sección XVI, Mexico City 14080, MexicoDouble-stranded RNA adenosine deaminase 1 (ADAR1) is significantly down-regulated in fibroblasts derived from Idiopathic Pulmonary Fibrosis (IPF) patients, and its overexpression restored levels of <i>miRNA-21</i>, <i>PELI1</i>, and <i>SPRY2</i>. There are two ADAR1 isoforms in humans, ADAR1-p110 and ADAR1-p150, generated by an alternative promoter. <i>Let-7d</i> is considered an essential microRNA in Pulmonary Fibrosis (PF). In silico analysis revealed <i>COL3A1</i> and <i>SMAD2</i>, proteins involved in the development of IPF, as <i>Let-7d</i> targets. We analyzed the role of ADAR1-p110 and ADAR1-p150 isoforms in the regulation of <i>Let-7d</i> maturation and the effect of this regulation on the expression of <i>COL3A1</i> and <i>SMAD2</i> in IPF fibroblast. We demonstrated that differential expression and subcellular distribution of ADAR1 isoforms in fibroblasts contribute to the up-regulation of <i>pri-miR-Let-7d</i> and down-regulation of mature <i>Let-7d</i>. Induction of overexpression of ADAR1 reestablishes the expression of <i>pri-miR-Let-7d</i> and <i>Let-7d</i> in lung fibroblasts. The reduction of mature <i>Let-7d</i> upregulates the expression of <i>COL3A1</i> and <i>SMAD2</i>. Thus, ADAR1 isoforms and <i>Let-7d</i> could have a synergistic role in IPF, which is a promising explanation in the mechanisms of fibrosis development, and the regulation of both molecules could be used as a therapeutic approach in IPF.https://www.mdpi.com/1422-0067/23/16/9028ADARRNA editionmiRNAIPF |
| spellingShingle | Gabriela Díaz-Piña Karla Rubio Rosa M. Ordoñez-Razo Guillermo Barreto Eduardo Montes Carina Becerril Alfonso Salgado Héctor Cabrera-Fuentes Arnoldo Aquino-Galvez Angeles Carlos-Reyes Victor Ruiz ADAR1 Isoforms Regulate <i>Let-7d</i> Processing in Idiopathic Pulmonary Fibrosis International Journal of Molecular Sciences ADAR RNA edition miRNA IPF |
| title | ADAR1 Isoforms Regulate <i>Let-7d</i> Processing in Idiopathic Pulmonary Fibrosis |
| title_full | ADAR1 Isoforms Regulate <i>Let-7d</i> Processing in Idiopathic Pulmonary Fibrosis |
| title_fullStr | ADAR1 Isoforms Regulate <i>Let-7d</i> Processing in Idiopathic Pulmonary Fibrosis |
| title_full_unstemmed | ADAR1 Isoforms Regulate <i>Let-7d</i> Processing in Idiopathic Pulmonary Fibrosis |
| title_short | ADAR1 Isoforms Regulate <i>Let-7d</i> Processing in Idiopathic Pulmonary Fibrosis |
| title_sort | adar1 isoforms regulate i let 7d i processing in idiopathic pulmonary fibrosis |
| topic | ADAR RNA edition miRNA IPF |
| url | https://www.mdpi.com/1422-0067/23/16/9028 |
| work_keys_str_mv | AT gabrieladiazpina adar1isoformsregulateilet7diprocessinginidiopathicpulmonaryfibrosis AT karlarubio adar1isoformsregulateilet7diprocessinginidiopathicpulmonaryfibrosis AT rosamordonezrazo adar1isoformsregulateilet7diprocessinginidiopathicpulmonaryfibrosis AT guillermobarreto adar1isoformsregulateilet7diprocessinginidiopathicpulmonaryfibrosis AT eduardomontes adar1isoformsregulateilet7diprocessinginidiopathicpulmonaryfibrosis AT carinabecerril adar1isoformsregulateilet7diprocessinginidiopathicpulmonaryfibrosis AT alfonsosalgado adar1isoformsregulateilet7diprocessinginidiopathicpulmonaryfibrosis AT hectorcabrerafuentes adar1isoformsregulateilet7diprocessinginidiopathicpulmonaryfibrosis AT arnoldoaquinogalvez adar1isoformsregulateilet7diprocessinginidiopathicpulmonaryfibrosis AT angelescarlosreyes adar1isoformsregulateilet7diprocessinginidiopathicpulmonaryfibrosis AT victorruiz adar1isoformsregulateilet7diprocessinginidiopathicpulmonaryfibrosis |