ArticleAmerican journal of respiratory cell and molecular biology2007
Thyroid transcription factor in differentiating type II cells: regulation, isoforms, and target genes.
Article in American journal of respiratory cell and molecular biology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 76 citations in OpenAlex.
- A comparative analysis of clinical phenotypes and outcomes in childhood interstitial lung disease due to surfactant dysfunction disorders: focusing on mutations in SFTPC, ABCA3, and NKX2-1 genes.Italian journal of pediatrics · 2025Article
- Bi-allelic LAMP3 variants in childhood interstitial lung disease: a surfactant-related disease.EBioMedicine · 2025Article
- Review
- Protective effect of recombinant interleukin-10 on newborn rat lungs exposed to short-term sublethal hyperoxia.Clinical and experimental pediatrics · 2024Article
- PRDM3/16 regulate chromatin accessibility required for NKX2-1 mediated alveolar epithelial differentiation and function.Nature communications · 2024Article
- Functional characterization of two novel NKX2-1 frameshift variants that cause pulmonary surfactant dysfunction.Pediatric research · 2024Article
- PRDM3/16 Regulate Chromatin Accessibility Required for NKX2-1 Mediated Alveolar Epithelial Differentiation and Function.bioRxiv : the preprint server for biology · 2023Article
- Thyroid transcription factor 1 (TTF-1) negativity as a predictor of unfavorable response to EGFR-TKI therapy in advanced lung adenocarcinoma patients with EGFR mutations.Thoracic cancer · 2023Article
- Rare surfactant-related variants in familial and sporadic pulmonary fibrosis.Human mutation · 2022Article
- Plasmid DNA for Therapeutic Applications in Cancer.Pharmaceutics · 2022Review
- Perspectives of future lung toxicology studies using human pluripotent stem cells.Archives of toxicology · 2022Review
- Transcription start site-level expression of thyroid transcription factor 1 isoforms in lung adenocarcinoma and its clinicopathological significance.The journal of pathology. Clinical research · 2021Article
- CRISPRi-mediated functional analysis of NKX2-1-binding sites in the lung.Communications biology · 2021Article
- Transcriptional control of lung alveolar type 1 cell development and maintenance by NK homeobox 2-1.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Thyroid transcription factor-1 as a prognostic indicator for stage IV lung adenocarcinoma with and without EGFR-sensitizing mutations.BMC cancer · 2019Article
- Encapsulated miR-200c and Nkx2.1 in a nuclear/mitochondria transcriptional regulatory network of non-metastatic and metastatic lung cancer cells.BMC cancer · 2019Article
- Identification of key candidate genes and miRNA‑mRNA target pairs in chronic lymphocytic leukemia by integrated bioinformatics analysis.Molecular medicine reports · 2019Article
- Expression of a novel surfactant protein gene is associated with sites of extrapulmonary respiration in a lungless salamander.Proceedings. Biological sciences · 2018Article
- Positional integration of lung adenocarcinoma susceptibility loci with primary human alveolar epithelial cell epigenomes.Epigenomics · 2018Article
- Mutations in the thyroid transcription factor gene NKX2-1 result in decreased expression of SFTPB and SFTPC.Pediatric research · 2018Article
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7 authors at 1 institution in 1 country.
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Abstract
Thyroid transcription factor-1 (TTF-1, product of the Nkx2.1 gene) is essential for branching morphogenesis of the lung and enhances expression of surfactant proteins by alveolar type II cells. We investigated expression of two TTF-1 mRNA transcripts, generated by alternative start sites and coding for 42- and 46-kD protein isoforms in the mouse, during hormone-induced differentiation of human fetal lung type II cells in culture. Transcript for 42-kD TTF-1 was 20-fold more abundant than TTF-1(46) mRNA by RT-PCR. Only 42-kD protein was detected in lung cells, and its content increased during in vivo development and in response to in vitro glucocorticoid plus cAMP treatment. To examine TTF-1 target proteins, recombinant, phosphorylated TTF-1(42) was expressed in nuclei of cells by adenovirus transduction. By microarray analysis, 14 genes were comparably induced by recombinant TTF-1 (rTTF-1) and hormone treatment, and 9 additional hormone-responsive genes, including surfactant proteins-A/B/C, were partially induced by rTTF-1. The most highly (approximately 10-fold) TTF-1-induced genes were DC-LAMP (LAMP3) and CEACAM6 with induction confirmed by Western analysis and immunostaining. Treatment of cells with hormones plus small inhibitory RNA directed toward TTF-1 reduced TTF-1 content by approximately 50% and inhibited hormone induction of the 23 genes induced by rTTF-1. In addition, knockdown of TTF-1 inhibited 72 of 274 other genes induced by hormones. We conclude that 42-kD TTF-1 is required for induction of a subset of regulated genes during type II cell differentiation.
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