ArticleAmerican journal of physiology. Lung cellular and molecular physiology2023
FGF18 promotes human lung branching morphogenesis through regulating mesenchymal progenitor cells.
Article in American journal of physiology. Lung cellular and molecular physiology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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9 citing papers in PubMed, 10 citations in OpenAlex.
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- Fibroblast Growth Factors in Lung Development and Regeneration: Mechanisms and Therapeutic Potential.Cells · 2025Review
- Elevated Senescence Markers in Developing Trisomy 21 Human Lungs.American journal of respiratory cell and molecular biology · 2025Article
- A multidisciplinary approach towards modeling of a virtual human lung.NPJ systems biology and applications · 2025Review
- Morphological and molecular aspects of lung development.Histology and histopathology · 2025Review
- VEGF-A isoforms induce the expression of APLN in endothelial cells during human prenatal lung development.Frontiers in cell and developmental biology · 2025Article
- Preferential FGF18/FGFR activity in pseudoglandular versus canalicular stage human lung fibroblasts.Frontiers in cell and developmental biology · 2023Article
- Altered Epithelial-Mesenchymal Progenitor States Lead to Matrix Deposition, Tissue Inflammation, and Transitional Epithelial State in Congenital Diaphragmatic Hernia.Fetal and pediatric pathologyArticle
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Authors and funding
8 authors at 5 institutions in 1 country.
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Abstract
Fibroblast growth factor (FGF) signaling is known to play an important role in lung organogenesis. However, we recently demonstrated that FGF10 fails to induce branching in human fetal lungs as is observed in mouse. Our previous human fetal lung RNA sequencing data exhibited increased FGF18 during the pseudoglandular stage of development, suggestive of its importance in human lung branching morphogenesis. Whereas it has been previously reported that FGF18 is critical during alveologenesis, few studies have described its implication in lung branching, specifically in human. Therefore, we aimed to determine the role of FGF18 in human lung branching morphogenesis. Human fetal lung explants within the pseudoglandular stage of development were treated with recombinant human FGF18 in air-liquid interface culture. Explants were analyzed grossly to assess differences in branching pattern, as well as at the cellular and molecular levels. FGF18 treatment promoted branching in explant cultures and demonstrated increased epithelial proliferation as well as maintenance of the double positive SOX2/SOX9 distal bud progenitor cells, confirming its role in human lung branching morphogenesis. In addition, FGF18 treated explants displayed increased expression of SOX9, FN1, and COL2A1 within the mesenchyme, all factors that are important to chondrocyte differentiation. In humans, cartilaginous airways extend deep into the lung up to the 12th generation of branching whereas in mouse these are restricted to the trachea and main bronchi. Therefore, our data suggest that FGF18 promotes human lung branching morphogenesis through regulating mesenchymal progenitor cells.
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