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. OBJECTIVES: 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.
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. OBJECTIVES: 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.
Authors: Patrick Y Jay; Malgorzata Bielinska; Jonathan M Erlich; Susanna Mannisto; William T Pu; Markku Heikinheimo; David B Wilson Journal: Dev Biol Date: 2006-10-05 Impact factor: 3.582
Authors: Kate G Ackerman; Jianlong Wang; Liqing Luo; Yuko Fujiwara; Stuart H Orkin; David R Beier Journal: Am J Respir Cell Mol Biol Date: 2006-12-01 Impact factor: 6.914
Authors: Hidehiko Nakanishi; Takahiro Sugiura; James B Streisand; Scott M Lonning; Jesse D Roberts Journal: Am J Physiol Lung Cell Mol Physiol Date: 2007-03-30 Impact factor: 5.464
Authors: Miguel A Alejandre-Alcázar; Grazyna Kwapiszewska; Irwin Reiss; Oana V Amarie; Leigh M Marsh; Julia Sevilla-Pérez; Malgorzata Wygrecka; Bastian Eul; Silke Köbrich; Mareike Hesse; Ralph T Schermuly; Werner Seeger; Oliver Eickelberg; Rory E Morty Journal: Am J Physiol Lung Cell Mol Physiol Date: 2006-10-27 Impact factor: 5.464