Am. J. Respir. Cell Mol. Biol., Vol 10, No. 6, 06 1994, 635-642.
Regulation of lung branching morphogenesis by bombesin-like peptides and neutral endopeptidase
SM Aguayo, WE Schuyler, JJ Murtagh Jr and J Roman
Department of Medicine, Atlanta Department of Veterans Affairs Medical Center, Decatur, GA 30033.
The expression of bombesin-like peptides (BLPs) by pulmonary neuroendocrine
cells is transiently upregulated during lung development. A functional role
for BLPs is supported by their ability to stimulate lung growth and
maturation both in vitro and in vivo during the late stages of lung
development. In addition, the cell membrane-associated enzyme CD10/neutral
endopeptidase 24.11 (CD10/NEP), which inactivates BLPs and other regulatory
peptides, is also expressed by developing lungs and modulates the
stimulatory effects of BLPs on lung growth and maturation. We hypothesized
that, in addition to expressing BLPs and CD10/NEP, embryonic lungs must
express BLP receptors, and that BLPs may also regulate processes that occur
during early lung development such as branching morphogenesis. Using
reverse transcriptase-polymerase chain reaction and oligonucleotide primers
designed for amplifying a BLP receptor originally isolated from Swiss 3T3
mouse fibroblasts, we found that embryonic mouse lungs express a similar
BLP receptor mRNA during the pseudoglandular stage of lung development when
branching morphogenesis take place. Subsequently, we evaluated the effects
of ligands for this BLP receptor using embryonic mouse lungs in an in vitro
model of lung branching morphogenesis. We found that, in comparison with
control lungs, treatment with bombesin (1 to 100 nM) resulted in a modest
increase in clefts or branching points. In contrast, embryonic mouse lungs
treated with the BLP analog [Leu13-psi(CH2NH)Leu14]bombesin (1 microM),
which also binds to this BLP receptor but has predominantly antagonistic
effects, demonstrated fewer branching points.(ABSTRACT TRUNCATED AT 250
WORDS)
