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Involvement of 4-hydroxy-2-nonenal in the pathogenesis of pulmonary fibrosis

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Abstract

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.

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Acknowledgements

This work was supported by a grant from CONACYT (project CB-287162) and by a grant from Secretary of Public Education (SEP), Strengthening program in Educational Quality 2018 & 2019 (PFCE). We thank Universidad Autónoma Benito Juárez de Oaxaca for all the administrative support.

Funding

Grant from CONACYT, project CB-287162 and grant from SEP, PFCE- 2018 & 2019.

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Authors and Affiliations

  1. Laboratorio de Fibrosis y Cáncer, Facultad de Medicina y Cirugía, Universidad Autónoma Benito Juárez de Oaxaca, Oaxaca, Mexico

    Edilburga Reyes-Jiménez, Alma Aurora Ramírez-Hernández, Jovito Cesar Santos-Álvarez & Juan Manuel Velázquez-Enríquez

  2. Centro de Investigación Facultad de Medicina, UNAM-UABJO, Oaxaca, Mexico

    Socorro Pina-Canseco

  3. CONACYT-Facultad de Medicina y Cirugía, Universidad Autónoma Benito Juárez de Oaxaca, Oaxaca, Mexico

    Rafael Baltiérrez-Hoyos & Verónica Rocío Vásquez-Garzón

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Reyes-Jiménez E, Ramírez-Hernández AA, Santos-Álvarez JC, Velázquez-Enríquez JM, and Pina-Canseco S performed the literature search and wrote the manuscript; Baltiérrez-Hoyos R supervised the writing and style correction of the manuscript; Vásquez-Garzón VR designed the project and supervised the writing and style correction of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Verónica Rocío Vásquez-Garzón.

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Reyes-Jiménez, E., Ramírez-Hernández, A., Santos-Álvarez, J. et al. Involvement of 4-hydroxy-2-nonenal in the pathogenesis of pulmonary fibrosis. Mol Cell Biochem 476, 4405–4419 (2021). https://doi.org/10.1007/s11010-021-04244-9

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