NF-kB induces lung maturation during mouse lung morphogenesis.
Lung maturation is hallmarked by the appearance of surfactant-producing alveoli during transition from the saccular to alveolar stage of lung development. Inflammation can disrupt this process and accelerate lung maturity following intrauterine amniotic infection (chorioamnionitis). Nuclear factor kB (NF-kB) is a transcription factor central to multiple inflammatory and developmental pathways, including dorsal-ventral patterning in fruit flies, limb and mammary and submandibular gland development in mice, and branching morphogenesis in chick lungs. Given its shared role in inflammation and developmental signaling, we hypothesized that overexpression of NF-kB targeted to the lung epithelium would exert maturational effects on alveolar development. We generated transgenic mice with lung-specific overexpression of the RelA subunit of NF-kB using a surfactant protein C promoter construct. Our results showed that RelA overexpression in the lung yields increased alveolar type I and type II cells. These findings are consistent with a model whereby NF-kB may induce maturation of lung development through decreased apoptosis of epithelial cells.
Londhe
Vedang A
VA
Department of Pediatrics, Division of Neonatology and Developmental Biology, David Geffen School of Medicine at UCLA, Los Angeles, California 90095-1752, USA. vlondhe@mednet.ucla.edu
Nguyen
Hanh T
HT
Jeng
Jade-Ming
JM
Li
Xia
X
Li
Changgong
C
Tiozzo
Caterina
C
Zhu
Nianling
N
Minoo
Parviz
P
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D051402:Aquaporin 5 / Q000378:metabolism; D015152:Blotting, Northern; D015153:Blotting, Western; D001973:Bromodeoxyuridine; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D036341:Intercellular Signaling Peptides and Proteins; D008168:Lung / Q000196:embryology* / Q000648:ultrastructure; D051379:Mice; D008822:Mice, Transgenic; D008855:Microscopy, Electron, Scanning; D009024:Morphogenesis / Q000502:physiology*; D009687:Nuclear Proteins / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D011486:Protein C / Q000235:genetics; D037721:Pulmonary Surfactant-Associated Protein C; D000074482:Thyroid Nuclear Factor 1; D051996:Transcription Factor RelA / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism
C496038:Aqp5 protein, mouse; D051402:Aquaporin 5; D036341:Intercellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D010455:Peptides; D011486:Protein C; D037721:Pulmonary Surfactant-Associated Protein C; C498144:Rela protein, mouse; C489680:Sftpc protein, mouse; D000074482:Thyroid Nuclear Factor 1; D051996:Transcription Factor RelA; D014157:Transcription Factors; D001973:Bromodeoxyuridine