Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Tlalpan 4502, 14080, Mexico City, CP, Mexico.
Instituto Nacional de Cancerología, Mexico City, Mexico.
Respir Res. 2019 Jun 24;20(1):130. doi: 10.1186/s12931-019-1100-4.
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.
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.
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.
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.
特发性肺纤维化（IPF）是一种与年龄相关的、进行性的、致命性疾病，其发病机制与产生过多细胞外基质积聚在肺实质中的成纤维细胞/肌成纤维细胞灶有关。缺氧已被描述为其发展和进展的决定因素。然而，该途径的不同成员的作用尚未完全描述。
通过 Western blot、定量 PCR、免疫组化和免疫细胞化学评估了 HIF alpha 亚基 1、2 和 3 异构体的表达及其在肺组织中和源自 IPF 患者的成纤维细胞系中的肌成纤维细胞分化中的作用。
缺氧信号通路在肺组织和 IPF 患者的成纤维细胞中非常活跃，这表现在 alpha 亚基 1 和 2 的丰度增加，这进一步与肌成纤维细胞标志物 αSMA 的表达增加相关。相比之下，HIF-3α的表达降低与其启动子高甲基化有关。
这项研究进一步支持缺氧在特发性肺纤维化发病机制中的作用，并提出 HIF-3α 的表达可能是这些现象的潜在负调节剂。
