TY - JOUR
T1 - Role of secretoglobin 3A2 in lung development
AU - Kurotani, Reiko
AU - Tomita, Takeshi
AU - Yang, Qian
AU - Carlson, Bradley A.
AU - Chen, Chi
AU - Kimura, Shioko
PY - 2008/8/15
Y1 - 2008/8/15
N2 - Rationale: 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. Objectives: 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. Measurements and Main Results: SCGB3A2 significantly promoted both early and late stages of lung development. Conclusions: SCGB3A2 is a novel growth factor in lung.
AB - Rationale: 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. Objectives: 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. Measurements and Main Results: SCGB3A2 significantly promoted both early and late stages of lung development. Conclusions: SCGB3A2 is a novel growth factor in lung.
KW - Fetal lung development
KW - Growth factor
KW - NKX2-1
KW - Secretoglobin 3A2
KW - Uteroglobin-related protein 1
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U2 - 10.1164/rccm.200707-1104OC
DO - 10.1164/rccm.200707-1104OC
M3 - Article
C2 - 18535256
AN - SCOPUS:48949102514
SN - 1073-449X
VL - 178
SP - 389
EP - 398
JO - American journal of respiratory and critical care medicine
JF - American journal of respiratory and critical care medicine
IS - 4
ER -