Dysregulated Expression of Hypoxia-inducible Factors Augments Myofibroblasts Differentiation in Idiopathic Pulmonary Fibrosis

Overview

Journal Respir Res

Specialty Pulmonary Medicine

Date 2019 Jun 26

PMID 31234835

Citations 30

Authors

Arnoldo Aquino-Galvez

Georgina Gonzalez-Avila

Laura Lorena Jimenez-Sanchez

Hector Aquiles Maldonado-Martinez

Jose Cisneros

Fernanda Toscano-Marquez

Manuel Castillejos-Lopez

Luz Maria Torres-Espindola

Rafael Velazquez-Cruz

Victor Hugo Olivera Rodriguez

Edgar Flores-Soto

Hector Solis-Chagoyan

Carlos Cabello

Joaquin Zuniga

Yair Romero

Affiliations

Soon will be listed here.

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.

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