{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"Research Square"}],"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T00:01:18Z","timestamp":1772236878809,"version":"3.50.1"},"posted":{"date-parts":[[2024,3,15]]},"group-title":"In Review","reference-count":0,"publisher":"Springer Science and Business Media LLC","license":[{"start":{"date-parts":[[2024,3,15]],"date-time":"2024-03-15T00:00:00Z","timestamp":1710460800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,5,1]]},"abstract":"<title>Abstract<\/title>\n                <p>\n                  Lung branching morphogenesis relies on intricate epithelial-mesenchymal interactions and signaling networks. Still, the interplay between signaling and energy metabolism in shaping embryonic lung development remains unexplored. Retinoic Acid (RA) signaling influences lung proximal-distal patterning and branching morphogenesis, but its role as metabolic modulator is unknown. Hence, this study investigates how RA signaling affects the metabolic profile of lung branching. We performed\n                  <italic>ex vivo<\/italic>\n                  lung explant culture of embryonic chicken lungs treated with DMSO, 1 \u00b5M RA, or 10 \u00b5M BMS493. Extracellular metabolite consumption\/production was evaluated by\n                  <sup>1<\/sup>\n                  H-NMR spectroscopy. Mitochondrial respiration and biogenesis were also analyzed. Proliferation was assessed using an EdU-based assay. The expression of crucial metabolic\/signaling components was examined through western blot, qPCR, and\n                  <italic>in situ<\/italic>\n                  hybridization. RA signaling stimulation redirects glucose towards pyruvate and succinate production rather than to alanine or lactate. Inhibition of RA signaling reduces lung branching, resulting in a cystic-like phenotype while promoting mitochondrial function. Here, RA signaling emerges as a regulator of tissue proliferation and lactate dehydrogenase expression. Furthermore, RA governs fatty acid metabolism through an AMPK-dependent mechanism. These findings underscore RA's pivotal role in shaping lung metabolism during branching morphogenesis, contributing to our understanding of lung development and cystic-related lung disorders.\n                <\/p>","DOI":"10.21203\/rs.3.rs-2883496\/v3","type":"posted-content","created":{"date-parts":[[2024,3,15]],"date-time":"2024-03-15T15:29:41Z","timestamp":1710516581000},"source":"Crossref","is-referenced-by-count":2,"title":["Retinoic Acid-mediated control of energy metabolism is essential for lung branching morphogenesis"],"prefix":"10.21203","author":[{"given":"Hugo","family":"Fernandes-Silva","sequence":"first","affiliation":[]},{"given":"Marco G.","family":"Alves","sequence":"additional","affiliation":[]},{"given":"Marcia R.","family":"Garcez","sequence":"additional","affiliation":[]},{"given":"Jorge","family":"Correia-Pinto","sequence":"additional","affiliation":[]},{"given":"Pedro F.","family":"Oliveira","sequence":"additional","affiliation":[]},{"given":"Catarina C. F.","family":"Homem","sequence":"additional","affiliation":[]},{"given":"Rute S.","family":"Moura","sequence":"additional","affiliation":[]}],"member":"297","container-title":[],"original-title":[],"link":[{"URL":"https:\/\/www.researchsquare.com\/article\/rs-2883496\/v3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.researchsquare.com\/article\/rs-2883496\/v3.html","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,6]],"date-time":"2024-05-06T20:36:21Z","timestamp":1715027781000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.researchsquare.com\/article\/rs-2883496\/v3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,15]]},"references-count":0,"URL":"https:\/\/doi.org\/10.21203\/rs.3.rs-2883496\/v3","relation":{"is-version-of":[{"id-type":"doi","id":"10.21203\/rs.3.rs-2883496\/v1","asserted-by":"subject"},{"id-type":"doi","id":"10.21203\/rs.3.rs-2883496\/v2","asserted-by":"subject"}],"is-preprint-of":[{"id-type":"doi","id":"10.3390\/ijms25095054","asserted-by":"subject"}],"has-version":[{"id-type":"doi","id":"10.21203\/rs.3.rs-2883496\/v1","asserted-by":"object"},{"id-type":"doi","id":"10.21203\/rs.3.rs-2883496\/v2","asserted-by":"object"}]},"subject":[],"published":{"date-parts":[[2024,3,15]]},"subtype":"preprint"}}