分析肺臟轉殖胎盤生長因子小鼠的肺臟發育(1/2)

After the widespread use of antenatal steroid, exogenous surfactant therapy, and improvements
in neonatal care, the survival rate of very low birth weight infants has increased, but
bronchopulmonary dysplasia (BPD) persists as one of the major complications in premature infants
who need prolonged ventilator support. The incidence of BPD ranges between 15 and 50%.
The etiology of BPD included the immaturity, prolonged oxygen therapy, barotrauma, and
infection. The pathological finding in the premature infants with BPD include alveolar hypoplasia,
vascular arrest and adaptive dysmorphic changes, and variable interstitial proliferation.
During the period of alveolarization, the lung also undergoes marked vascular growth as
reflected by the 20-fold increase in alveolar and capillary surface areas from birth to adulthood.
Mechanisms that increase vascular surface area during late gestation and the early postnatal period
are poorly understood, but it is clear that coordination of distal air space and vascular growth is
essential for normal lung development.
Vascular endothelial growth factor (VEGF) family has been found to play an important role in
vascuogenesis and angiogenesis. It has been well established that disrupted pulmonary vasculature
and decreased VEGF and Flt-1, but no changes in Flk-1, in human infants dying with BPD.
However, the role of PlGF, another ligand of Flt-1, in lung development is unknown. In our
previous study, we found that overexpression of PlGF, using CMV promotor, seems disrupt
pulmonary alveolarization. It give us a hint that PlGF may play an important role in lung
development.
In this year, we have used lung-specific promotor, SP-C (a gift from Dr. Whitsett, University of
Cincinnati), to successfully generated four different SP-C-PlGF transgenic lines with different
mRNA expression levels, confirmed by real time RT-PCR. In addition, we also demonstrated that
exogenous recombinant PlGF promoted type II pneumocytes cell death and inhibited cell
proliferation in vitro. In the next year, we will try to demonstrate the phenotype of this transgenic
mouse and setup the animal model for chronic lung disease.