Dysregulated expression of hypoxia-inducible factors augments myofibroblasts differentiation in idiopathic pulmonary fibrosis

Respiratory Research

  ^{1    1    1    1    1    1    2    3    4    5    6    7    8    8    9} 

[1] 0000 0000 8515 3604, grid.419179.3, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Tlalpan 4502, 14080, Mexico City, CP, Mexico;0000 0000 8515 3604, grid.419179.3, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Tlalpan 4502, 14080, Mexico City, CP, Mexico;0000 0001 2159 0001, grid.9486.3, Facultad de Ciencias, Universidad Nacional Autónoma México, Mexico City, Mexico;0000 0000 8515 3604, grid.419179.3, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Tlalpan 4502, 14080, Mexico City, CP, Mexico;0000 0001 2203 4701, grid.419886.a, Escuela de medicina y ciencias de la salud, Tecnologico de Monterrey, Mexico City, Mexico;0000 0001 2159 0001, grid.9486.3, Departamento de Farmacologia, Facultad de Medicina, Universidad Nacional Autónoma México, Mexico City, Mexico;0000 0001 2159 0001, grid.9486.3, Facultad de Ciencias, Universidad Nacional Autónoma México, Mexico City, Mexico;0000 0004 1773 4473, grid.419216.9, Instituto Nacional de Pediatría, Mexico City, Mexico;0000 0004 1776 9908, grid.419154.c, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, Mexico City, Mexico;0000 0004 1777 1207, grid.419167.c, Instituto Nacional de Cancerología, Mexico City, Mexico;0000 0004 1791 0836, grid.415745.6, Instituto Nacional de Medicina Genómica, Mexico City, Mexico;

关键词: Hypoxia inducible factors;    αSMA;    Lung fibroblasts;    HIF-1α;    HIF-2α;    HIF-3α;    Methylation;   

DOI  :  10.1186/s12931-019-1100-4

来源: publisher

【 摘 要 】

BackgroundIdiopathic 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.MethodsBy 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.ResultsHypoxia 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.ConclusionsThis 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.

【 授权许可】

CC BY