{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T13:02:56Z","timestamp":1791378176994,"version":"4.3.2"},"reference-count":189,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,5,31]],"date-time":"2025-05-31T00:00:00Z","timestamp":1748649600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"CONAHCYT","award":["194162"],"award-info":[{"award-number":["194162"]}]},{"name":"Instituto Nacional de Enfermedades Respiratorias Ismael Cos\u00edo Villegas","award":["194162"],"award-info":[{"award-number":["194162"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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-\u03b2 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.<\/jats:p>","DOI":"10.3390\/ijms26115302","type":"journal-article","created":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T11:40:32Z","timestamp":1748864432000},"page":"5302","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["The Hypoxia\u2013Retinoid Axis in Idiopathic Pulmonary Fibrosis: Multifaceted Etiology and Therapeutic Potential"],"prefix":"10.3390","volume":"26","author":[{"given":"Daniel","family":"Paz-Gomez","sequence":"first","affiliation":[{"name":"Laboratorio de Investigaci\u00f3n en Enfermedades Reum\u00e1ticas, Instituto Nacional de Enfermedades Respiratorias, Ismael Cos\u00edo Villegas (INER), Mexico City 14080, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8689-9755","authenticated-orcid":false,"given":"Manuel","family":"Castillejos-L\u00f3pez","sequence":"additional","affiliation":[{"name":"Unidad de Epidemiolog\u00eda Hospitalaria e Infectolog\u00eda, Instituto Nacional de Enfermedades Respiratorias Ismael Cos\u00edo Villegas (INER), Mexico City 14080, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8707-025X","authenticated-orcid":false,"given":"Yair","family":"Romero","sequence":"additional","affiliation":[{"name":"Facultad de Ciencias, Universidad Nacional Aut\u00f3noma de M\u00e9xico (UNAM), Mexico City 04510, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2649-8751","authenticated-orcid":false,"given":"Edgar","family":"Flores-Soto","sequence":"additional","affiliation":[{"name":"Departamento de Farmacolog\u00eda, 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