Molecular and Cellular Biochemistry ( IF 3.5 ) Pub Date : 2021-08-31 , DOI: 10.1007/s11010-021-04244-9 Edilburga Reyes-Jiménez 1 , Alma Aurora Ramírez-Hernández 1 , Jovito Cesar Santos-Álvarez 1 , Juan Manuel Velázquez-Enríquez 1 , Socorro Pina-Canseco 2 , Rafael Baltiérrez-Hoyos 3 , Verónica Rocío Vásquez-Garzón 3
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Pulmonary fibrosis is a chronic progressive disease with high incidence, prevalence, and mortality rates worldwide. It is characterized by excessive accumulation of extracellular matrix in the lung parenchyma. The cellular and molecular mechanisms involved in its pathogenesis are complex, and some are still unknown. Several studies indicate that oxidative stress, characterized by overproduction of 4-hydroxy-2-nonenal (4-HNE), is an important player in pulmonary fibrosis. 4-HNE is a highly reactive compound derived from polyunsaturated fatty acids that can react with proteins, phospholipids, and nucleic acids. Thus, many of the altered cellular mechanisms that contribute to this disease can be explained by the participation of 4-HNE. Here, we summarize the current knowledge on the molecular states and signal transduction pathways that contribute to the pathogenesis of pulmonary fibrosis. Furthermore, we describe the participation of 4-HNE in various mechanisms involved in pulmonary fibrosis development, with a focus on the cell populations involved in the initiation, development, and maintenance of the fibrotic process, mainly alveolar cells, endothelial cells, macrophages, and inflammatory cells. Due to its characteristic activity as a second messenger, 4-HNE, in addition to being a consequence of oxidative stress, can support maintenance of the inflammatory and fibrotic process by spreading the effects of reactive oxygen species (ROS). Thus, regulation of 4-HNE levels could be a viable strategy to reduce its effects on the mechanisms involved in pulmonary fibrosis development.
Graphic abstract
中文翻译：
4-羟基-2-壬烯醛在肺纤维化发病机制中的作用
肺纤维化是一种慢性进行性疾病，在全球范围内具有高发病率、患病率和死亡率。它的特征是肺实质中细胞外基质的过度积累。其发病机制涉及的细胞和分子机制很复杂，有些仍是未知的。几项研究表明，以过量产生 4-羟基-2-壬烯醛 (4-HNE) 为特征的氧化应激是肺纤维化的重要因素。4-HNE 是一种源自多不饱和脂肪酸的高反应性化合物，可与蛋白质、磷脂和核酸发生反应。因此，导致这种疾病的许多改变的细胞机制可以通过 4-HNE 的参与来解释。这里，我们总结了目前关于导致肺纤维化发病机制的分子状态和信号转导途径的知识。此外，我们描述了 4-HNE 参与肺纤维化发展的各种机制，重点关注参与纤维化过程的起始、发展和维持的细胞群，主要是肺泡细胞、内皮细胞、巨噬细胞和炎症细胞。由于其作为第二信使的特征活性，4-HNE 除了是氧化应激的结果外，还可以通过传播活性氧 (ROS) 的作用来支持炎症和纤维化过程的维持。因此，调节 4-HNE 水平可能是一种可行的策略，以减少其对参与肺纤维化发展的机制的影响。
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