ArticleRespiratory research2020
ROBO2 signaling in lung development regulates SOX2/SOX9 balance, branching morphogenesis and is dysregulated in nitrofen-induced congenital diaphragmatic hernia.
Article in Respiratory research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 21 citations in OpenAlex.
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- Role of Csdc2 in Regulating Secondary Hair Follicle Growth in Cashmere Goats.International journal of molecular sciences · 2024Article
- SOX on tumors, a comfort or a constraint?Cell death discovery · 2024Review
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- Chemogenetic activation of ventral medullary astrocytes enhances feeding and corticosterone release in response to mild glucoprivation.American journal of physiology. Regulatory, integrative and comparative physiology · 2023Article
- Intraluminal chloride regulates lung branching morphogenesis: involvement of PIEZO1/PIEZO2.Respiratory research · 2023Article
- NLRP3 Inflammasome Mediates Silica-induced Lung Epithelial Injury and Aberrant Regeneration in Lung Stem/Progenitor Cell-derived Organotypic Models.International journal of biological sciences · 2023Article
- Treatment with Amniotic Fluid Stem Cell Extracellular Vesicles Promotes Fetal Lung Branching and Cell Differentiation at Canalicular and Saccular Stages in Experimental Pulmonary Hypoplasia Secondary to Congenital Diaphragmatic Hernia.Stem cells translational medicine · 2022Article
- Distinct Epithelial Cell Profiles in Normal Versus Induced-Congenital Diaphragmatic Hernia Fetal Lungs.Frontiers in pediatrics · 2022Article
- 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
3 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundCharacterized by abnormal lung growth or maturation, congenital diaphragmatic hernia (CDH) affects 1:3000 live births. Cellular studies report proximal (SOX2
methodsThe expression profile for receptors and epithelial progenitor markers were assessed by Western blot and immunohistochemistry in a nitrofen-induced CDH rat model. Immunohistochemistry signals by pulmonary structure were also quantified from embryonic-to-saccular stages in normal and hypoplastic lungs. Ex vivo lung explant cultures were harvested at E13.5, cultures during 4 days and treated with increasing doses of recombinant rat ROBO1 or human ROBO2 Fc Chimera proteins for ROBO1 and ROBO2 inhibition, respectively. The lung explants were analyzed morphometrically and ROBO1, ROBO2, SOX2, SOX9, BMP4, and β-Catenin were quantified by Western blot.
resultsExperimental-CDH induces distinct expression profiles by pulmonary structure and developmental stage for both receptors (ROBO1 and ROBO2) and epithelial progenitor markers (SOX2 and SOX9) that provide evidence of the impairment of proximodistal patterning in experimental-CDH. Ex vivo functional studies showed unchanged branching morphogenesis after ROBO1 inhibition; increased fetal lung growth after ROBO2 inhibition in a mechanism-dependent on SOX2 depletion and overexpression of SOX9, non-phospho β-Catenin, and BMP4.
conclusionsThese studies provided evidence of receptors and epithelial progenitor cells which are severely affected by CDH-induction from embryonic-to-saccular stages and established the ROBO2 inhibition as promoter of branching morphogenesis through SOX2/SOX9 balance.
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