ArticlePediatric research2018
Mutations in the thyroid transcription factor gene NKX2-1 result in decreased expression of SFTPB and SFTPC.
Article in Pediatric research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00014859 (Epidemiology of Surfactant Protein-B Deficiency), which is not on this map. Cited by 13 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Epidemiology of Surfactant Protein-B Deficiency
Who cites it
13 citing papers in PubMed, 59 citations in OpenAlex.
- The Impact of Genetics on Pediatric Interstitial Lung Diseases: A Narrative Literature Review and Clinical Implications.Biomedicines · 2026Review
- Single-cell sequencing and organoids: applications in organ development and disease.Molecular biomedicine · 2025Review
- Genetic Disorders of Surfactant Metabolism.NeoReviews · 2025Review
- Origin and stepwise evolution of vertebrate lungs.Nature ecology & evolution · 2025Article
- Case Report: Hydroxychloroquine in an infant withFrontiers in pediatrics · 2025Article
- GCN5L1 regulates pulmonary surfactant production by modulating lamellar body biogenesis and trafficking in mouse alveolar epithelial cells.Cellular & molecular biology letters · 2023Article
- Article
- Organoid modeling of human fetal lung alveolar development reveals mechanisms of cell fate patterning and neonatal respiratory disease.Cell stem cell · 2023Article
- scTenifoldKnk: An efficient virtual knockout tool for gene function predictions via single-cell gene regulatory network perturbation.Patterns (New York, N.Y.) · 2022Article
- Surfactant protein disorders in childhood interstitial lung disease.European journal of pediatrics · 2021Review
- Is Progression of Pulmonary Fibrosis due to Ventilation-induced Lung Injury?American journal of respiratory and critical care medicine · 2019Review
- Genetic causes of surfactant protein abnormalities.Current opinion in pediatrics · 2019Review
- Localization of Secretory Mucins MUC5AC and MUC5B in Normal/Healthy Human Airways.American journal of respiratory and critical care medicine · 2019Article
Corrections and comments
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Authors and funding
7 authors at 5 institutions in 1 country.
Funding
Abstract
backgroundMutations in the NK2 homeobox 1 (NKX2-1) gene are associated with lung disease in infants and children. We hypothesize that disruption of normal surfactant gene expression with these mutations contributes to the respiratory phenotypes observed.
methodsTo assess transactivational activity, cotransfection of luciferase reporter vectors containing surfactant protein B or C (SFTPB or SFTPC) promoters with NKX2-1 plasmids was performed and luciferase activity was measured. To assess the binding of mutated proteins to target DNA, electrophoretic mobility shift assays (EMSA) were performed using nuclear protein labeled with oligonucleotide probes representing NKX2-1 consensus binding sequences followed by gel electrophoresis. The effect of overexpression of wild-type (WT) and mutant NKX2-1 on SFTPB and SFTPC was evaluated with quantitative real-time PCR.
resultsDecreased transactivation of the SFTPB promoter by both mutants and decreased transactivation of the SFTPC promoter by the L197P mutation was observed. EMSA demonstrated decreased DNA binding of both mutations to NKX2-1 consensus binding sequences. Transfection of A549 cells with NKX2-1 expression vectors demonstrated decreased stimulation of SFTPB and SFTPC expression by mutant proteins compared with that of WT.
conclusionDisruption of transcriptional activation of surfactant protein genes by these DNA-binding domain mutations is a plausible biological mechanism for disruption of surfactant function and subsequent respiratory distress.
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