Placental growth factor (PGF) is a member of the vascular endothelial growth factor (VEGF) family and plays a key role in angiogenesis, vasculogenesis, and tissue repair. PGF is primarily expressed in placental trophoblasts during pregnancy and contributes to pathological conditions such as cancer, rheumatoid arthritis, and cardiovascular disease by promoting angiogenesis. Unlike VEGF-A, PGF selectively binds to VEGFR-1 (Flt-1) and regulates vascular permeability and endothelial cell proliferation. PGF is involved in both physiological and pathological processes, making it a promising therapeutic target.
Human PGF adenoviral particles are genetically engineered viral vectors designed to deliver the PGF gene to target cells for research or therapeutic applications. Adenoviruses are a preferred choice for gene delivery due to their high transduction efficiency, broad tropism, and ability to infect both dividing and non-dividing cells. These viral particles are replication-defective, which prevents uncontrolled viral spread, thus ensuring safety. Adenoviral vectors carry human PGF under the control of a strong promoter, enabling stable and transient expression in host cells.
Here, the researchers investigated the effects of placental growth factor (PGF) overexpression and hyperoxia on lung development in neonatal rats and determined whether anti-PGF antibodies could improve hyperoxia-mediated lung development disorders in neonatal rats. After 7 days of normoxic culture, Normoxia neonatal rats were intraperitoneally or intratracheally injected with saline, adenovirus negative control (Ad-NC), or adenovirus-PGF (Ad-PGF) to form Normoxia groups, Normoxia + Ad-NC groups, and Normoxia + Ad-PGF groups. Hyperoxic neonatal rats were intraperitoneally injected with saline or anti-PGF antibodies to form Hyperoxia groups and Hyperoxia + anti-PGF groups. The results showed that the levels of PGF and its receptor Flt-1 in the lung tissues of neonatal rats in the Normoxia + Ad-PGF group and the Hyperoxia group were significantly increased. PGF overexpression in these groups led to lung injury in neonatal rats, and anti-PGF antibody treatment could significantly cure the lung injury caused by hyperoxia. In addition, PGF overexpression significantly increased TNF-α and Il-6 levels in bronchoalveolar lavage fluid (BAL) in both Normoxia + Ad-PGF and Hyperoxia groups. Immunohistochemical analysis showed that PGF overexpression and hyperoxia treatment significantly increased the expression of angiogenic marker CD34. However, its expression was significantly reduced after administration of anti-PGF antibody (compared with the hyperoxia control group). In conclusion, PGF overexpression impairs lung development in neonatal rats, while inhibition of its expression using anti-PGF antibody improves lung development.
Here, the researchers took lung tissues of newborn rats for IHC detection of CD34 expression, and the results showed that the CD34 expression level in lung tissues of rats in the Normoxia + Ad-PGF group was significantly higher than that in the Normoxia + Ad-NC group (Figure 1). In addition, the CD34 expression level in lung tissues of rats in the hyperoxia group was higher than that in the Normoxia group, while the CD34 expression level in lung tissues of rats in the Hyperoxia + anti-PGF group was significantly lower than that in the Hyperoxia group.
Figure 1. CD34 expression was detected by immunohistochemistry in lung tissues from newborn rats of each indicated group (n=10). (Zhang Z, et al., 2020)
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Consistent In Vivo Performance
Successfully used these adenoviral particles in mouse models. The in vivo expression was strong and stable, making them ideal for translational studies.
United Kingdom
02/02/2022
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