Abstract
This study investigates the effect of the overexpression of the placental growth factor (PGF) and hyperoxia on lung development and determines whether anti-PGF antibody ameliorates hyperoxia-mediated impairment of lung development in newborn rats. After exposure to normoxic conditions for seven days, newborn rats subjected to normoxia were intraperitoneally or intratracheally injected with physiological saline, adenovirus-negative control (Ad-NC), or adenovirus-PGF (Ad-PGF) to create the Normoxia, Normoxia+Ad-NC, and Normoxia+Ad-PGF groups, respectively. Newborn rats subjected to hyperoxia were intraperitoneally injected with physiological saline or anti-PGF antibodies to create the Hyperoxia and Hyperoxia+anti-PGF groups, respectively. Our results revealed significant augmentation in the levels of PGF and its receptor Flt-1 in the lung tissues of newborn rats belonging to the Normoxia+Ad-PGF or Hyperoxia groups. PGF overexpression in these groups caused lung injury in newborn rats, while anti-PGF antibody treatment significantly cured the hyperoxia-induced lung injury. Moreover, PGF overexpression significantly increased TNF-α and Il-6 levels in the bronchoalveolar lavage (BAL) fluid of the Normoxia+Ad-PGF and Hyperoxia groups. However, their levels were significantly reduced in the BAL fluid of the Hyperoxia+anti-PGF group. Immunohistochemical analysis revealed that PGF overexpression and hyperoxia treatment significantly increased the expression of the angiogenesis marker, CD34. However, its expression was significantly decreased upon administration of anti-PGF antibodies (compared to the control group under hyperoxia). In conclusion, PGF overexpression impairs lung development in newborn rats while its inhibition using an anti-PGF antibody ameliorates the same. These results provided new insights for the clinical management of bronchopulmonary dysplasia in premature infants.
Highlights
Bronchopulmonary dysplasia (BPD) is a major cause of chronic lung disease and is a serious sequela in preterm infants [1]
The lung tissues of newborn rats exposed to the respective experimental conditions were collected and western blot analysis was performed to observe the expression of Placental growth factor (PGF) and Flt1
It was observed that there was a significant increase in the expression of PGF and Flt1 in the lung tissues of the Normoxia+Ad-PGF group compared to that in the Normoxia+adenovirus-negative control (Ad-negative control (NC)) group (Figure 2)
Summary
Bronchopulmonary dysplasia (BPD) is a major cause of chronic lung disease and is a serious sequela in preterm infants [1] It causes poor developmental and clinical outcomes in very-low-birth-weight infants (weighing less than 1500 g by the age of 1 year) [2], resulting in long-term respiratory impairment and abnormal neurodevelopment [3]. These consequences extend beyond childhood and result in increased health care costs. Abman proposed a vascular hypothesis, according to which disruption of angiogenesis during lung development can impair the normal growth of lungs, resulting in decreased alveolarization and pulmonary arterial density [7]. Inhibiting the function of PGF may help in the management of the abnormal pulmonary vascular development in BPD cases, improving the symptoms of BPD
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