Effect of Hypoxia in the Transcriptomic Profile of Lung Fibroblasts from Idiopathic Pulmonary Fibrosis
Yair Romero,
Yalbi Itzel Balderas-Martínez,
Miguel Angel Vargas-Morales,
Manuel Castillejos-López,
Joel Armando Vázquez-Pérez,
Jazmín Calyeca,
Luz María Torres-Espíndola,
Nelly Patiño,
Angel Camarena,
Ángeles Carlos-Reyes,
Edgar Flores-Soto,
Guadalupe León-Reyes,
Martha Patricia Sierra-Vargas,
Iliana Herrera,
Erika Rubí Luis-García,
Víctor Ruiz,
Rafael Velázquez-Cruz,
Arnoldo Aquino-Gálvez
Affiliations
Yair Romero
Facultad de Ciencias, Universidad Nacional Autónoma México (UNAM), Mexico City 04510, Mexico
Yalbi Itzel Balderas-Martínez
Laboratorio de Biología Computacional, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas (INER), Mexico City 14080, Mexico
Miguel Angel Vargas-Morales
Laboratorio de Biología Molecular, Departamento de Fibrosis Pulmonar, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas (INER), Mexico City 14080, Mexico
Manuel Castillejos-López
Departamento de Epidemiología y Estadística, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas (INER), Mexico City 14080, Mexico
Joel Armando Vázquez-Pérez
Laboratorio de Biología Molecular de Enfermedades Emergentes y EPOC, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas (INER), Mexico City 14080, Mexico
Jazmín Calyeca
Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH 43210, USA
Luz María Torres-Espíndola
Laboratorio de Farmacología, Instituto Nacional de Pediatría (INP), Mexico City 04530, Mexico
Nelly Patiño
Unidad de Citometría de Flujo (UCiF), Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City 14610, Mexico
Angel Camarena
Laboratorio de HLA, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas (INER), Mexico City 14080, Mexico
Ángeles Carlos-Reyes
Laboratorio de Onco-Inmunobiología, Departamento de Enfermedades Crónico-Degenerativas, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas (INER), Mexico City 14080, Mexico
Edgar Flores-Soto
Departamento de Farmacología, Facultad de Medicina, Universidad Nacional Autónoma de México (UNAM), Mexico City 04510, Mexico
Guadalupe León-Reyes
Laboratorio de Genómica del Metabolismo Óseo, Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City 14610, Mexico
Martha Patricia Sierra-Vargas
Departamento de Investigación en Toxicología y Medicina Ambiental, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas (INER), Mexico City 14080, México
Iliana Herrera
Laboratorio de Biología Celular, Departamento de Fibrosis Pulmonar, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas (INER), Mexico City 14080, Mexico
Erika Rubí Luis-García
Laboratorio de Biología Celular, Departamento de Fibrosis Pulmonar, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas (INER), Mexico City 14080, Mexico
Víctor Ruiz
Laboratorio de Biología Molecular, Departamento de Fibrosis Pulmonar, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas (INER), Mexico City 14080, Mexico
Rafael Velázquez-Cruz
Laboratorio de Genómica del Metabolismo Óseo, Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City 14610, Mexico
Arnoldo Aquino-Gálvez
Laboratorio de Biología Molecular, Departamento de Fibrosis Pulmonar, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas (INER), Mexico City 14080, Mexico
Idiopathic pulmonary fibrosis (IPF) is an aging-associated disease characterized by exacerbated extracellular matrix deposition that disrupts oxygen exchange. Hypoxia and its transcription factors (HIF-1α and 2α) influence numerous circuits that could perpetuate fibrosis by increasing myofibroblasts differentiation and by promoting extracellular matrix accumulation. Therefore, this work aimed to elucidate the signature of hypoxia in the transcriptomic circuitry of IPF-derived fibroblasts. To determine this transcriptomic signature, a gene expression analysis with six lines of lung fibroblasts under normoxia or hypoxia was performed: three cell lines were derived from patients with IPF, and three were from healthy donors, a total of 36 replicates. We used the Clariom D platform, which allows us to evaluate a huge number of transcripts, to analyze the response to hypoxia in both controls and IPF. The control′s response is greater by the number of genes and complexity. In the search for specific genes responsible for the IPF fibroblast phenotype, nineteen dysregulated genes were found in lung fibroblasts from IPF patients in hypoxia (nine upregulated and ten downregulated). In this sense, the signaling pathways revealed to be affected in the pulmonary fibroblasts of patients with IPF may represent an adaptation to chronic hypoxia.