Paz-Gomez Daniel, Castillejos-López Manuel, Romero Yair, Flores-Soto Edgar, Romero-Martinez Bianca S, Vázquez-Pérez Joel Armando, Gonzalez-Avila Georgina, Ruiz Victor, Carlos-Reyes Ángeles, Velázquez-Cruz Rafael, Choreño-Parra José Alberto, Lara-Lemus Roberto, Rojas-Duran Fausto, Martínez Briseño David, Zuñiga Joaquín, Torres-Espíndola Luz María, Aquino-Gálvez Arnoldo
Laboratorio de Investigación en Enfermedades Reumáticas, Instituto Nacional de Enfermedades Respiratorias, Ismael Cosío Villegas (INER), Mexico City 14080, Mexico.
Unidad de Epidemiología Hospitalaria e Infectología, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas (INER), Mexico City 14080, Mexico.
Int J Mol Sci. 2025 May 31;26(11):5302. doi: 10.3390/ijms26115302.
Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal lung disease with limited therapeutic options. This review focuses on the role of retinoids, particularly all-trans retinoic acid (atRA), and hypoxia in the pathogenesis of IPF. Despite an established understanding of genetic and environmental factors in IPF, the interplay between retinoid signaling and the response to hypoxia remains poorly explored due to its complexity. Preclinical evidence suggests that atRA could help reduce pulmonary fibrosis by modulating TGF-β signaling pathways and epithelial-to-mesenchymal transition (EMT). Additionally, we mention other diseases where a relationship between hypoxia and retinoids has been observed. We review how hypoxia, a key factor in the progression of IPF, may influence the efficacy of retinoid therapy. Combination strategies are explored to overcome hypoxia-induced treatment resistance. Finally, we address the complex role of retinoids in lung regeneration, balancing their potential benefits against the risk of exacerbating fibrotic processes. This review suggests that retinoids have potential as a treatment or adjuvant for IPF and highlights the need for further research to elucidate the precise mechanisms of retinoid action in IPF, particularly in hypoxia.
特发性肺纤维化（IPF）是一种进行性致命性肺部疾病，治疗选择有限。本综述重点关注视黄酸，尤其是全反式维甲酸（atRA）以及缺氧在IPF发病机制中的作用。尽管对IPF中的遗传和环境因素已有既定认识，但由于视黄酸信号传导与缺氧反应之间的相互作用复杂，其仍未得到充分探索。临床前证据表明，atRA可通过调节转化生长因子-β（TGF-β）信号通路和上皮-间质转化（EMT）来帮助减轻肺纤维化。此外，我们还提及了其他已观察到缺氧与视黄酸之间存在关联的疾病。我们综述了缺氧这一IPF进展中的关键因素可能如何影响视黄酸治疗的疗效。探讨了联合策略以克服缺氧诱导的治疗抵抗。最后，我们阐述了视黄酸在肺再生中的复杂作用，权衡其潜在益处与加剧纤维化过程风险之间的关系。本综述表明，视黄酸有潜力作为IPF的治疗方法或辅助治疗手段，并强调需要进一步研究以阐明视黄酸在IPF中，尤其是在缺氧情况下的确切作用机制。
