Dysregulated expression of hypoxia-inducible factors augments myofibroblasts differentiation in idiopathic pulmonary fibrosis
Dysregulated expression of hypoxia-inducible factors augments myofibroblasts differentiation in idiopathic pulmonary fibrosis
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DOI：
10.1186/s12931-019-1100-4
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发表时间：
2019-06-24
影响因子：
5.8
通讯作者：
Romero, Yair
中科院分区：
文献类型：
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作者：
Aquino-Galvez, Arnoldo;Gonzalez-Avila, Georgina;Romero, Yair
特发性肺纤维化（IPF）是一种与年龄相关的、进行性的、致死性的疾病，其发病机制与成纤维细胞/肌成纤维细胞灶导致细胞外基质在肺实质内过度积聚有关。缺氧已被描述为其发展和进展的决定性因素。方法采用Western blot、定量PCR、免疫组化和免疫组化等方法，检测HIF α亚型1、2和3的表达，结果发现低氧信号通路在肺组织和IPF成纤维细胞中非常活跃患者，如通过α亚基1和2的丰度所证明的，其进一步与肌成纤维细胞标志物SMA的表达增加相关。与此相反，HIF-3表现出降低表达与其启动子hypermethylation.ConclusionsThis study lends进一步支持缺氧参与IPF的发病机制，并提出HIF-3表达作为一个潜在的负调节这些现象。
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.