Dysregulated expression of hypoxia-inducible factors augments myofibroblasts differentiation in idiopathic pulmonary fibrosis
Por:
Aquino-Galvez, Arnoldo, Gonzalez-Avila, Georgina, Lorena Jimenez-Sanchez, Laura, Aquiles Maldonado-Martinez, Hector, Cisneros, Jose, Toscano-Marquez, Fernanda, Castillejos-Lopez, Manuel, Maria Torres-Espindola, Luz, Velazquez-Cruz, Rafael, Olivera Rodriguez, Victor Hugo, Flores-Soto, Edgar, Solis-Chagoyan, Hector, Cabello, Carlos, Zuniga, Joaquin, Romero, Yair
Publicada:
24 jun 2019
Categoría:
Pulmonary and respiratory medicine
Resumen:
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 SMA. In contrast, HIF-3
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-3
expression as a potential negative regulator of these phenomena.
Filiaciones:
Inst Nacl Enfermedades Resp Ismael Cosio Villegas, Tlalpan 4502, Mexico City 14080, DF, Mexico
Inst Nacl Cancerol, Mexico City, DF, Mexico
Univ Nacl Autonoma Mexico, Fac Ciencias, Mexico City, DF, Mexico
Inst Nacl Pediat, Mexico City, DF, Mexico
Inst Nacl Med Genom, Mexico City, DF, Mexico
Univ Nacl Autonoma Mexico, Fac Med, Dept Farmacol, Mexico City, DF, Mexico
Inst Nacl Psiquiatria Ramon de la Fuente Muniz, Mexico City, DF, Mexico
Tecnol Monterrey, Escuela Med & Ciencias Salud, Mexico City, DF, Mexico
Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Tlalpan 4502, 14080, Mexico City, CP, Mexico.
Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Tlalpan 4502, 14080, Mexico City, CP, Mexico
Instituto Nacional de Cancerología, Mexico City, Mexico
Universidad Nacional Autónoma México, Facultad de Ciencias, Mexico City, Mexico
Instituto Nacional de Pediatría, México City, Mexico
Instituto Nacional de Medicina Genómica, Mexico City, Mexico
Departamento de Farmacologia, Facultad de Medicina, Universidad Nacional Autónoma México, Mexico City, Mexico
Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, Mexico City, Mexico
Escuela de Medicina y Ciencias de la Salud, Tecnologico de Monterrey, Mexico City, Mexico
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