title: Expression of thyroid transcription factor-1, surfactant proteins, type I cell-associated antigen, and Clara cell secretory protein in pulmonary hypoplasia.
abstract: Pulmonary hypoplasia (PH) is a developmental abnormality characterized by diminished distal lung parenchyma. Recent studies have demonstrated that thyroid transcription factor 1 (TTF-1), a member of NKx2 family of homeodomain transcription factors, plays an important role in lung organogenesis and lung epithelial gene expression. In order to evaluate whether abnormal expression of TTF-1 contributes to the pathophysiology of PH, we studied the expression of TTF-1, as well as that of the surfactant proteins (SPs), Clara cell secretory protein (CCSP), and type I cell-associated antigen (T1 cell-Ag), in PH. Immunolocalization patterns of these proteins were evaluated in 15 cases of PH with different associated diseases and compared with those of 14 matched controls. Our study demonstrated that the concentration gradient of TTF-1 along the proximal-distal axis in normal fetal lung is disrupted in PH after 24 weeks gestational age, while the expression of the SPs, CCSP, and T1 cell-Ag seemed to be preserved. We conclude that a normal TTF-1 expression pattern might be crucial in the control of distal lung development. Failure to switch off expression of TTF-1 in PH of more than 24 weeks gestational age may be a final common pathway leading to PH associated with the disease processes investigated in this study.
authors.affiliation: Department of Pathology, New York University Medical Center, 560 First Avenue, New York, NY 10016, USA.
authors.forename: H
authors.initials: H
authors.lastname: Zhou
authors.forename: R A
authors.initials: RA
authors.lastname: Morotti
authors.forename: S A
authors.initials: SA
authors.lastname: Profitt
authors.forename: C
authors.initials: C
authors.lastname: Langston
authors.forename: S E
authors.initials: SE
authors.lastname: Wert
authors.forename: J A
authors.initials: JA
authors.lastname: Whitsett
authors.forename: M A
authors.initials: MA
authors.lastname: Greco
mesh_terms: D004847:Epithelial Cells / Q000378:metabolism; D005865:Gestational Age; D006801:Humans; D007124:Immunoenzyme Techniques; D007231:Infant, Newborn; D008168:Lung / Q000002:abnormalities*; D009687:Nuclear Proteins / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D011510:Proteolipids / Q000378:metabolism*; D011650:Pulmonary Alveoli / Q000166:cytology / Q000378:metabolism; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000378:metabolism*; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000378:metabolism*; D014598:Uteroglobin
chemical_list: C000614412:NKX2-1 protein, human; D009687:Nuclear Proteins; D011506:Proteins; D011510:Proteolipids; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; C556389:SCGB1A1 protein, human; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors; D014598:Uteroglobin