Dysregulated expression of hypoxia-inducible factors augments myofibroblasts differentiation in idiopathic pulmonary fibrosis
Abstract Background Idiopathic pulmonary fibrosis (IPF) is an age-related, progressive and lethal disease, whose pathogenesis is associated with fibroblasts/myofibroblasts foci that produce excessive extracellular matrix accumulation in lung parenchyma. Hypoxia has been described as a determinant fa...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2019-06-01
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| Series: | Respiratory Research |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12931-019-1100-4 |
| _version_ | 1818318462665097216 |
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| author | Arnoldo Aquino-Gálvez Georgina González-Ávila Laura Lorena Jiménez-Sánchez Héctor Aquiles Maldonado-Martínez José Cisneros Fernanda Toscano-Marquez Manuel Castillejos-López Luz María Torres-Espíndola Rafael Velázquez-Cruz Víctor Hugo Olivera Rodríguez Edgar Flores-Soto Héctor Solís-Chagoyán Carlos Cabello Joaquín Zúñiga Yair Romero |
| author_facet | Arnoldo Aquino-Gálvez Georgina González-Ávila Laura Lorena Jiménez-Sánchez Héctor Aquiles Maldonado-Martínez José Cisneros Fernanda Toscano-Marquez Manuel Castillejos-López Luz María Torres-Espíndola Rafael Velázquez-Cruz Víctor Hugo Olivera Rodríguez Edgar Flores-Soto Héctor Solís-Chagoyán Carlos Cabello Joaquín Zúñiga Yair Romero |
| author_sort | Arnoldo Aquino-Gálvez |
| collection | DOAJ |
| description | Abstract Background Idiopathic pulmonary fibrosis (IPF) is an age-related, progressive and lethal disease, whose pathogenesis is associated with fibroblasts/myofibroblasts foci that produce excessive extracellular matrix accumulation in lung parenchyma. Hypoxia has been described as a determinant factor in its development and progression. However, the role of distinct members of this pathway is not completely described. Methods By western blot, quantitative PCR, Immunohistochemistry and Immunocitochemistry were evaluated, the expression HIF alpha subunit isoforms 1, 2 & 3 as well, as their role in myofibroblast differentiation in lung tissue and fibroblast cell lines derived from IPF patients. Results Hypoxia signaling pathway was found very active in lungs and fibroblasts from IPF patients, as demonstrated by the abundance of alpha subunits 1 and 2, which further correlated with the increased expression of myofibroblast marker αSMA. In contrast, HIF-3α showed reduced expression associated with its promoter hypermethylation. Conclusions This study lends further support to the involvement of hypoxia in the pathogenesis of IPF, and poses HIF-3α expression as a potential negative regulator of these phenomena. |
| first_indexed | 2024-12-13T09:53:36Z |
| format | Article |
| id | doaj.art-e3dc8ac2bc604c88985687516ed68d7b |
| institution | Directory Open Access Journal |
| issn | 1465-993X |
| language | English |
| last_indexed | 2024-12-13T09:53:36Z |
| publishDate | 2019-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Respiratory Research |
| spelling | doaj.art-e3dc8ac2bc604c88985687516ed68d7b2022-12-21T23:51:51ZengBMCRespiratory Research1465-993X2019-06-0120111010.1186/s12931-019-1100-4Dysregulated expression of hypoxia-inducible factors augments myofibroblasts differentiation in idiopathic pulmonary fibrosisArnoldo Aquino-Gálvez0Georgina González-Ávila1Laura Lorena Jiménez-Sánchez2Héctor Aquiles Maldonado-Martínez3José Cisneros4Fernanda Toscano-Marquez5Manuel Castillejos-López6Luz María Torres-Espíndola7Rafael Velázquez-Cruz8Víctor Hugo Olivera Rodríguez9Edgar Flores-Soto10Héctor Solís-Chagoyán11Carlos Cabello12Joaquín Zúñiga13Yair Romero14Instituto Nacional de Enfermedades Respiratorias Ismael Cosío VillegasInstituto Nacional de Enfermedades Respiratorias Ismael Cosío VillegasInstituto Nacional de Enfermedades Respiratorias Ismael Cosío VillegasInstituto Nacional de CancerologíaInstituto Nacional de Enfermedades Respiratorias Ismael Cosío VillegasFacultad de Ciencias, Universidad Nacional Autónoma MéxicoInstituto Nacional de Enfermedades Respiratorias Ismael Cosío VillegasInstituto Nacional de PediatríaInstituto Nacional de Medicina GenómicaInstituto Nacional de CancerologíaDepartamento de Farmacologia, Facultad de Medicina, Universidad Nacional Autónoma MéxicoInstituto Nacional de Psiquiatría Ramón de la Fuente MuñizInstituto Nacional de Enfermedades Respiratorias Ismael Cosío VillegasInstituto Nacional de Enfermedades Respiratorias Ismael Cosío VillegasInstituto Nacional de Enfermedades Respiratorias Ismael Cosío VillegasAbstract Background Idiopathic pulmonary fibrosis (IPF) is an age-related, progressive and lethal disease, whose pathogenesis is associated with fibroblasts/myofibroblasts foci that produce excessive extracellular matrix accumulation in lung parenchyma. Hypoxia has been described as a determinant factor in its development and progression. However, the role of distinct members of this pathway is not completely described. Methods By western blot, quantitative PCR, Immunohistochemistry and Immunocitochemistry were evaluated, the expression HIF alpha subunit isoforms 1, 2 & 3 as well, as their role in myofibroblast differentiation in lung tissue and fibroblast cell lines derived from IPF patients. Results Hypoxia signaling pathway was found very active in lungs and fibroblasts from IPF patients, as demonstrated by the abundance of alpha subunits 1 and 2, which further correlated with the increased expression of myofibroblast marker αSMA. In contrast, HIF-3α showed reduced expression associated with its promoter hypermethylation. Conclusions This study lends further support to the involvement of hypoxia in the pathogenesis of IPF, and poses HIF-3α expression as a potential negative regulator of these phenomena.http://link.springer.com/article/10.1186/s12931-019-1100-4Hypoxia inducible factors; αSMALung fibroblastsHIF-1αHIF-2αHIF-3αMethylation |
| spellingShingle | Arnoldo Aquino-Gálvez Georgina González-Ávila Laura Lorena Jiménez-Sánchez Héctor Aquiles Maldonado-Martínez José Cisneros Fernanda Toscano-Marquez Manuel Castillejos-López Luz María Torres-Espíndola Rafael Velázquez-Cruz Víctor Hugo Olivera Rodríguez Edgar Flores-Soto Héctor Solís-Chagoyán Carlos Cabello Joaquín Zúñiga Yair Romero Dysregulated expression of hypoxia-inducible factors augments myofibroblasts differentiation in idiopathic pulmonary fibrosis Respiratory Research Hypoxia inducible factors; αSMA Lung fibroblasts HIF-1α HIF-2α HIF-3α Methylation |
| title | Dysregulated expression of hypoxia-inducible factors augments myofibroblasts differentiation in idiopathic pulmonary fibrosis |
| title_full | Dysregulated expression of hypoxia-inducible factors augments myofibroblasts differentiation in idiopathic pulmonary fibrosis |
| title_fullStr | Dysregulated expression of hypoxia-inducible factors augments myofibroblasts differentiation in idiopathic pulmonary fibrosis |
| title_full_unstemmed | Dysregulated expression of hypoxia-inducible factors augments myofibroblasts differentiation in idiopathic pulmonary fibrosis |
| title_short | Dysregulated expression of hypoxia-inducible factors augments myofibroblasts differentiation in idiopathic pulmonary fibrosis |
| title_sort | dysregulated expression of hypoxia inducible factors augments myofibroblasts differentiation in idiopathic pulmonary fibrosis |
| topic | Hypoxia inducible factors; αSMA Lung fibroblasts HIF-1α HIF-2α HIF-3α Methylation |
| url | http://link.springer.com/article/10.1186/s12931-019-1100-4 |
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