Expression of Transcription Factor GATA-6 in Alveolar Epithelial Cells Is Linked to Neonatal Lung Disease.
BACKGROUND
Premature birth and respiratory distress syndrome (RDS) are risk factors for disturbed lung development and bronchopulmonary dysplasia (BPD). The molecular mechanisms related to prematurity and BPD remain largely unknown. Epithelial expression of the transcription factor GATA-6 has been implicated in normal and abnormal murine lung development.


OBJECTIVE
The possible involvement of GATA-6 in the normal development and in RDS and BPD was investigated in the human and baboon lung.


METHODS
Immunohistochemistry was used to study the expression of GATA-6 and thyroid transcription factor 1 in lung specimens from different age groups of human and baboon fetuses and newborns with lung disease. Furthermore, the regulatory role of TGF-β₁ in GATA-6 expression was investigated in human pulmonary epithelial cell lines using RT-PCR.


RESULTS
GATA-6 expression increased in the developing human airway epithelium along with advancing gestation, but diminished to negligible at birth. In RDS, GATA-6 expression was enhanced at 5-7 days after birth, and decreased thereafter. In BPD, the expression of GATA-6 in alveolar epithelial cells was low. These results were confirmed and extended using an established baboon model of prematurity. The in vitro experiments revealed that TGF-β₁ induces GATA-6 and thyroid transcription factor 1 expression in lung epithelial cells.


CONCLUSIONS
Our results suggest that the expression of GATA-6 at the early stages of the preterm lung may be related to impaired postnatal alveolar development.
Children's Hospital, University of Helsinki, Helsinki, Finland.
Riika
R
Vähätalo
Tiina M
TM
Asikainen
Riitta
R
Karikoski
Vuokko L
VL
Kinnula
Carl W
CW
White
Sture
S
Andersson
Markku
M
Heikinheimo
Marjukka
M
Myllärniemi
D000818:Animals; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D005333:Fetus; D050993:GATA6 Transcription Factor / Q000096:biosynthesis* / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007231:Infant, Newborn; D007234:Infant, Premature / Q000502:physiology*; D008297:Male; D010215:Papio; D011650:Pulmonary Alveoli / Q000166:cytology / Q000378:metabolism / Q000503:physiopathology*; D012313:RNA / Q000737:chemistry / Q000235:genetics; D012127:Respiratory Distress Syndrome, Newborn / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors
D004268:DNA-Binding Proteins; D050993:GATA6 Transcription Factor; C504003:TTF1 protein, human; D014157:Transcription Factors; D012313:RNA