scholarly journals Gene Structure and Expression of Human Thyroid Transcription Factor-1 in Respiratory Epithelial Cells

1995 ◽  
Vol 270 (14) ◽  
pp. 8108-8114 ◽  
Author(s):  
Kazushige Ikeda ◽  
Jean C. Clark ◽  
Jessica R. Shaw-White ◽  
Mildred T. Stahlman ◽  
Christopher J. Boutell ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Epithelial Cells ◽  
Gene Structure ◽  
Human Thyroid ◽  
Respiratory Epithelial Cells ◽  
Thyroid Transcription Factor 1 ◽  
Thyroid Transcription Factor ◽  
Gene Structure And Expression ◽  
Respiratory Epithelial ◽  
Transcription Factor 1

scholarly journals Modulation of Thyroid-Specific Gene Expression in Normal and Nodular Human Thyroid Tissues from Adults: An in Vivo Effect of Thyrotropin

2005 ◽  
Vol 90 (10) ◽  
pp. 5692-5697 ◽  
Author(s):  
Rocco Bruno ◽  
Elisabetta Ferretti ◽  
Emanuele Tosi ◽  
Franco Arturi ◽  
Paolo Giannasio ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Human Thyroid ◽  
Normal Tissues ◽  
Thyroid Transcription Factor 1 ◽  
Thyroid Transcription Factor ◽  
Group 2 ◽  
Transcription Factor 1 ◽  
Tsh Levels

Context: Evidence from in vitro studies or animal models has shown that TSH affects thyrocytes by thyroid-specific expression modulation. Objective: The objective of our study was to analyze the role of TSH in human thyroid gene expression in vivo. Design/Setting: Thirty-nine normal thyroid tissues were collected at the same center. Study Subjects: Patients were divided into two groups based on serum TSH levels: 17 with normal TSH levels (1–4 mU/liter; group 1) and 22 with TSH levels below 0.5 mU/liter (group 2). Intervention: Group 2 underwent thyroidectomy after suppressive l-T4 therapy. Main Outcome Measures: mRNA levels of thyroid genes such as sodium/iodide symporter (NIS), apical iodide transporter, pendrin, thyroglobulin, thyroperoxidase, TSH receptor, paired box transcription factor 8, and thyroid transcription factor-1 were evaluated by quantitative PCR. Results: The reduction of TSH stimulation causes decreases in NIS and apical iodide transporter gene expression in normal tissues and more limited reductions in thyroglobulin, thyroperoxidase, and paired box transcription factor 8, but it has no significant effect on TSH receptor, pendrin, or thyroid transcription factor-1. Comparison of NIS levels in normal and nodular tissues from the same patient confirmed that it is differentially expressed in nodules only in the presence of normal TSH (P < 0.01). In patients with suppressed TSH, nodular NIS levels were similar to those in normal tissues. Conclusions: Our data represent the first demonstration in human thyroid tissues that TSH contributes to the regulation of thyrocyte differentiation by modulating thyroid gene levels. It exerts a particularly important effect on the transcription of NIS, which becomes very low after prolonged TSH suppression.

scholarly journals Nuclear localization domain of thyroid transcription factor-1 in respiratory epithelial cells

1997 ◽  
Vol 328 (3) ◽  
pp. 757-761 ◽  
Author(s):  
Manely GHAFFARI ◽  
Xin ZENG ◽  
A. Jeffrey WHITSETT ◽  
Cong YAN
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Epithelial Cells ◽  
Nuclear Localization ◽  
Nuclear Translocation ◽  
Surfactant Protein ◽  
Thyroid Transcription Factor 1 ◽  
Surfactant Protein B ◽  
Thyroid Transcription Factor ◽  
Transcription Factor 1

Thyroid transcription factor-1 (TITF-1) is a homeodomain containing transcription factor that binds to and selectively activates the expression of genes in thyroid and pulmonary epithelial cells. TITF-1 plays a critical role in gene expression and in organogenesis of lung and thyroid. In the present work, epitope-tagged TITF-1 proteins were used to identify the regions of the TITF-1 polypeptide that mediate nuclear localization and transcriptional activity in human lung adenocarcinoma cells. A series of TITF-1-flag deletion mutants was generated and transfected into H441 cells to determine amino acid sequences involved in translocation to the nucleus. Transfection of the TITF-1-flag mutants demonstrated that a nuclear localization signal (NLS) sequence, located at the N-terminus of the homeodomain, is critical for nuclear targeting. The NLS was essential but not sufficient for translocation of TITF-1 to the nucleus, since deletion of the homeodomain itself also blocked nuclear translocation in the presence of NLS. Deletion of the N-terminal transactivation domain of TITF-1 completely abolished its transcriptional activation on the human surfactant protein-B promoter, and deletion of the C-terminal domain partially reduced its stimulatory activity. Nuclear translocation of TITF-1 depends on both an NLS and the homeodomain of the polypeptide. Both C- and N-terminal regions of TITF-1 are involved in transactivation of surfactant protein B gene expression in pulmonary cells.

scholarly journals Hepatocyte nuclear factor 3 activates transcription of thyroid transcription factor 1 in respiratory epithelial cells.

1996 ◽  
Vol 16 (7) ◽  
pp. 3626-3636 ◽  
Author(s):  
K Ikeda ◽  
J R Shaw-White ◽  
S E Wert ◽  
J A Whitsett
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Family Members ◽  
Nuclear Proteins ◽  
Nuclear Factor ◽  
Hepatocyte Nuclear Factor ◽  
Thyroid Transcription Factor 1 ◽  
Thyroid Transcription Factor ◽  
Respiratory Epithelial ◽  
Transcription Factor 1

Thyroid transcription factor 1 (TTF-1), hepatocyte nuclear factor 3alpha (HNF-3alpha), and HNF-3beta regulate the transcription of genes expressed in the respiratory epithelium. To test whether members of the HNF-3/forkhead family influence TTF-1 gene expression, deletion constructs containing the 5' region of the human TTF-1 gene were transfected into immortalized mouse lung epithelial (MLE) cells. DNase I protection and electrophoretic mobility shift assays identified elements in the 5' region of the TTF-1 gene that bound MLE cell nuclear proteins consistent with the binding of HNF-3 to sites at positions -135 to -124 and -14 to -3. In MLE cells, TTF-1-luciferase reporter constructs were activated by cotransfection with HNF-3beta, activated to a lesser extent by HNF-3alpha, but not activated by HFH-8. HNF-3alpha. and HFH-8 inhibited the activation of TTF-1-luciferase by HNF-3beta. Site-specific mutagenesis of each of the HNF-3 binding sites in the human TTF-1 gene inhibited the binding of MLE cell nuclear proteins and inhibited transactivation of the TTF-1-luciferase constructs after cotransfection with HNF-3beta. Immunohistochemical staining demonstrated that both HNF-3beta and TTF-1 were detected in bronchiolar and alveolar type II cells in the human lung. Modulation of TTF-1 gene expression by members of the HNF-3/forkhead family members may provide a mechanism by which distinct HNF-3/forkhead family members influence respiratory epithelial cell gene expression and cell differentiation.

Expression of Thyroid Transcription Factor-1 in Congenital Cystic Adenomatoid Malformation of the Lung

2000 ◽  
Vol 3 (5) ◽  
pp. 455-461 ◽  
Author(s):  
Raffaella A. Morotti ◽  
Maria C. Gutierrez ◽  
Fred Askin ◽  
Sherri A. Profitt ◽  
Susan E. Wert ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Epithelial Cells ◽  
Gestational Age ◽  
Congenital Cystic Adenomatoid Malformation ◽  
Type Ii Cells ◽  
Type Ii ◽  
Basal Cells ◽  
Thyroid Transcription Factor 1 ◽  
Thyroid Transcription Factor ◽  
Transcription Factor 1

Congenital cystic adenomatoid malformation (CCAM) is an abnormality of branching morphogenesis of the lung. CCAM types 1, 2, and 3 exhibit a cellular composition that is different from that of CCAM type 4 when evaluated with bronchiolar and alveolar cell markers. Thyroid transcription factor 1 (TTF-1) regulates early lung development. To evaluate the potential role of TTF-1 in the development of CCAM, TTF-1 expression in CCAM was compared to that of fetal lungs at varying gestational ages. Twenty-three CCAM cases (17 type 1, two type 2, two type 3, and two type 4) and 11 fetal lungs (3 pseudoglandular, 4 canalicular, and 4 terminal sac stages) were analyzed using a rabbit polyclonal antiserum to rat TTF-1. Nuclear staining for TTF-1 was observed in ciliated and nonciliated cells of the bronchial and bronchiolar epithelia and in cells lining the distal air spaces by 12 weeks gestational age. By mid-gestation, proximal bronchial cells were TTF-1 negative, except for the basal cells, while TTF-1 staining was maintained in distal bronchiolar and alveolar cells. TTF-1 expression decreased in both bronchial, bronchiolar, and alveolar epithelia with advancing gestational age and cytodifferentiation. At term, TTF-1 expression persisted in a few bronchial and bronchiolar basal cells and in all alveolar type II cells, whereas type I cells were negative. In CCAM, TTF-1 was detected in the nuclei of epithelial cells lining the cysts. TTF-1 was expressed in a majority of the bronchiolar-like epithelial cells of the cysts in CCAM types 1, 2, and 3, where almost 100% of the cells were TTF-1 positive. In contrast, TTF-1 expression in the alveolar-like epithelium of CCAM type 4 cysts was restricted to type II cells and only 30%–60% of the lining cells were TTF-1 positive. These results support the hypothesis that CCAM types 1, 2, and 3 reflect abnormalities in lung morphogenesis and differentiation that are distinct from those for CCAM type 4. The role played by TTF-1 in the development of CCAM, if any, is not clear.

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