{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T08:23:15Z","timestamp":1787732595782,"version":"build-2784847793"},"reference-count":97,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p>\n                    Wnt signaling coordinates lung specification, alveolar maturation, adult epithelial maintenance, and injury repair, but its biological output varies with developmental or disease stage, anatomical compartment, responding cell type, receptor context, and signal duration. This review organizes current evidence using a temporal-spatial framework that links Wnt ligands and receptors to source and responding cells, downstream canonical or noncanonical pathways, interacting signaling networks, and cellular outcomes. During development, mesenchymal Wnt2\/2\u00a0b\u2013\u03b2-catenin signaling specifies pulmonary endoderm, whereas canonical and noncanonical Wnt programs subsequently regulate distal progenitor expansion, branching geometry, epithelial differentiation, secondary septation, pulmonary microvascular maturation, and postnatal lung growth; maintenance of an\n                    <jats:italic>AXIN2<\/jats:italic>\n                    <jats:sup>+<\/jats:sup>\n                    alveolar type 2 (AT2) progenitor niche becomes a distinct function in the adult lung. After adult alveolar injury, Wnt activity is dynamically remodeled as AT2 cells proliferate and traverse damage-associated transient progenitor and keratin 8-positive (KRT8\n                    <jats:sup>+<\/jats:sup>\n                    ) transitional states before restoring the alveolar type 1 cell layer. This framework helps reconcile apparently discordant observations in chronic lung diseases. Bronchopulmonary dysplasia disrupts Wnt timing during alveologenesis; chronic obstructive pulmonary disease can combine deficient canonical Wnt responsiveness in the alveolar compartment with Wnt5a-associated inhibition of repair and distinct airway Wnt activation; and idiopathic pulmonary fibrosis features persistent Wnt-transforming growth factor-\u03b2 signaling in abnormal epithelial and fibroblast niches. Therapeutic translation should therefore avoid indiscriminate pathway activation or inhibition and instead pursue reversible, local, biomarker-guided modulation matched to disease stage, cellular compartment, receptor profile, dose, and duration.\n                  <\/jats:p>","DOI":"10.3389\/fcell.2026.1914253","type":"journal-article","created":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T08:14:05Z","timestamp":1787732045000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Temporal regulation of wnt signaling in alveolar development and regeneration: mechanistic insights and therapeutic advances in chronic lung diseases"],"prefix":"10.3389","volume":"14","author":[{"given":"Mingyue","family":"Ren","sequence":"first","affiliation":[{"name":"Department of Pediatrics, The First Affiliated Hospital of Henan University of Chinese Medicine","place":["Zhengzhou, Henan, China"]},{"name":"School of Pediatrics, Henan University of Chinese Medicine","place":["Zhengzhou, Henan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guihua","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The First Affiliated Hospital of Henan University of Chinese Medicine","place":["Zhengzhou, Henan, China"]},{"name":"School of Pediatrics, Henan University of Chinese Medicine","place":["Zhengzhou, Henan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The First Affiliated Hospital of Henan University of Chinese Medicine","place":["Zhengzhou, Henan, China"]},{"name":"School of Pediatrics, Henan University of Chinese Medicine","place":["Zhengzhou, Henan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suping","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The First Affiliated Hospital of Henan University of Chinese Medicine","place":["Zhengzhou, Henan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The First Affiliated Hospital of Henan University of Chinese Medicine","place":["Zhengzhou, Henan, China"]},{"name":"School of Pediatrics, Henan University of Chinese Medicine","place":["Zhengzhou, Henan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengmeng","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The First Affiliated Hospital of Henan University of Chinese Medicine","place":["Zhengzhou, Henan, China"]},{"name":"School of Pediatrics, Henan University of Chinese Medicine","place":["Zhengzhou, Henan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingxue","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The First Affiliated Hospital of Henan University of Chinese Medicine","place":["Zhengzhou, Henan, China"]},{"name":"School of Pediatrics, Henan University of Chinese Medicine","place":["Zhengzhou, Henan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1186\/s12889-024-17686-9","article-title":"Estimating the global prevalence of chronic obstructive pulmonary disease (COPD): a systematic review and meta-analysis","volume":"24","author":"Al Wachami","year":"2024","journal-title":"BMC Public Health"},{"key":"B2","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1165\/rcmb.2013-0346OC","article-title":"Inhibition of \u03b2-catenin signaling improves alveolarization and reduces pulmonary hypertension in experimental bronchopulmonary dysplasia","volume":"51","author":"Alapati","year":"2014","journal-title":"Am. 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