TY - JOUR
T1 - Prenatal administration of neuropeptide bombesin promotes lung development in a rat model of nitrofen-induced congenital diaphragmatic hernia
AU - Sakai, Kohei
AU - Kimura, Osamu
AU - Furukawa, Taizo
AU - Fumino, Shigehisa
AU - Higuchi, Koji
AU - Wakao, Junko
AU - Kimura, Koseki
AU - Aoi, Shigeyoshi
AU - Masumoto, Kouji
AU - Tajiri, Tatsuro
N1 - Funding Information:
This work was supported by Grant-in-Aid for Exploratory Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT KAKENHI grant number 22659318 ).
Publisher Copyright:
© 2014 Elsevier Inc. All rights reserved.
PY - 2014/12/1
Y1 - 2014/12/1
N2 - Background/purpose Fetal medical treatment to improve lung hypoplasia in congenital diaphragmatic hernia (CDH) has yet to be established. The neuropeptide bombesin (BBS) might play an important role in lung development. The present study aims to determine whether prenatally administered BBS could be useful to promote fetal lung development in a rat model of nitrofen-induced CDH. Methods Pregnant rats were administered with nitrofen (100 mg) on gestation day 9.5 (E9.5). BBS (50 mg/kg/day) was then daily infused intraperitoneally from E14, and fetal lungs were harvested on E21. The expression of PCNA was assessed by both immunohistochemical staining and RT-PCR to determine the amount of cell proliferation. Lung maturity was assessed as the expression of TTF-1, a marker of alveolar epithelial cell type II. Results The lung-body-weight ratio was significantly increased in CDH/BBS(+) compared with CDH/BBS(-) (p < 0.05). The number of cells stained positive for PCNA and TTF-1 was significantly decreased in CDH/BBS(+) compared with CDH/BBS(-) (p < 0.01). The TTF-1 mRNA expression levels were significantly decreased in CDH/BBS(+) compared with CDH/BBS(-) (p < 0.05). Conclusions Prenatally administered BBS promotes lung development in a rat model of nitrofen-induced CDH. Neuropeptide BBS could help to rescue lung hypoplasia in fetal CDH.
AB - Background/purpose Fetal medical treatment to improve lung hypoplasia in congenital diaphragmatic hernia (CDH) has yet to be established. The neuropeptide bombesin (BBS) might play an important role in lung development. The present study aims to determine whether prenatally administered BBS could be useful to promote fetal lung development in a rat model of nitrofen-induced CDH. Methods Pregnant rats were administered with nitrofen (100 mg) on gestation day 9.5 (E9.5). BBS (50 mg/kg/day) was then daily infused intraperitoneally from E14, and fetal lungs were harvested on E21. The expression of PCNA was assessed by both immunohistochemical staining and RT-PCR to determine the amount of cell proliferation. Lung maturity was assessed as the expression of TTF-1, a marker of alveolar epithelial cell type II. Results The lung-body-weight ratio was significantly increased in CDH/BBS(+) compared with CDH/BBS(-) (p < 0.05). The number of cells stained positive for PCNA and TTF-1 was significantly decreased in CDH/BBS(+) compared with CDH/BBS(-) (p < 0.01). The TTF-1 mRNA expression levels were significantly decreased in CDH/BBS(+) compared with CDH/BBS(-) (p < 0.05). Conclusions Prenatally administered BBS promotes lung development in a rat model of nitrofen-induced CDH. Neuropeptide BBS could help to rescue lung hypoplasia in fetal CDH.
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U2 - 10.1016/j.jpedsurg.2014.09.015
DO - 10.1016/j.jpedsurg.2014.09.015
M3 - Article
C2 - 25487476
AN - SCOPUS:84916243416
VL - 49
SP - 1749
EP - 1752
JO - Journal of Pediatric Surgery
JF - Journal of Pediatric Surgery
SN - 0022-3468
IS - 12
ER -