Role of secretoglobin 3A2 in lung development.
BACKGROUND
Secretoglobin 3A2 (SCGB3A2) was originally identified as a downstream target in lung for the homeodomain transcription factor NKX2-1, whose null mutation resulted in severely hypoplastic lungs. A very low level of SCGB3A2 is expressed in lungs at Embryonic Day (E) 11.5 during mouse development, which markedly increases by E16.5, the time when lung undergoes dramatic morphologic changes, suggesting that SCGB3A2 may be involved in lung development in addition to a known role in lung inflammation.


OBJECTIVE
To determine whether SCGB3A2 plays a role in lung development.


METHODS
To assess a potential role for SCGB3A2 during early lung development, wild-type and Nkx2-1-null fetal lungs of early developmental stages were subjected to ex vivo organ culture in the presence of SCGB3A2. Nkx2-1-null fetuses were exposed to SCGB3A2 during early organogenesis period through intravenous administration of this protein to Nkx2-1-heterozygous pregnant females carrying these null fetuses. Cultured lungs and fetal lungs were subjected to histologic and immunohistochemical analyses. To assess a role for SCGB3A2 in late lung development, SCGB3A2 was administered to pregnant wild-type females during mid- to late organogenesis stages, and the preterm pups and/or their lungs were evaluated for extent of maturity using breathing motion, gross morphology and histology of lungs, expression of gestational stage-specific genes, and phospholipid profiles.


RESULTS
SCGB3A2 significantly promoted both early and late stages of lung development.


CONCLUSIONS
SCGB3A2 is a novel growth factor in lung.
Laboratory of Metabolism, Laboratory of Cancer Prevention, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Reiko
R
Kurotani
Takeshi
T
Tomita
Qian
Q
Yang
Bradley A
BA
Carlson
Chi
C
Chen
Shioko
S
Kimura
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D005260:Female; D005325:Fetal Organ Maturity / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D005865:Gestational Age; D008168:Lung / Q000196:embryology* / Q000473:pathology; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D009924:Organ Culture Techniques; D038081:Organogenesis / Q000235:genetics*; D011247:Pregnancy; D011506:Proteins / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D060765:Secretoglobins; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000235:genetics*
C000614414:Nkx2-1 protein, mouse; D009687:Nuclear Proteins; D011506:Proteins; C449818:Scgb3a2 protein, mouse; D060765:Secretoglobins; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors