The role of placenta growth factor in the hyperoxia‐induced acute lung injury in an animal model

Abstract

Prolonged exposure to hyperoxia leads to acute lung injury. Alveolar type II cells are main target of hyperoxia-induced lung injury. However, the cellular and molecular mechanisms remain unknown. Here, we aimed to investigate the role of placental growth factor (PLGF) in hyperoxia-induced lung injury. Using experimental hyperoxia-induced lung injury model of neonatal rat and mouse lung epithelial type II cells (MLE-12), we examined the levels of PLGF in bronchoalveolar lavage fluid and in the supernatants of MLE-12 cells. Our results revealed that exogenous PLGF induced hyperoxia-induced lung injury. Furthermore, PLGF triggered a shift of vinculin from insoluble to soluble cell fraction, similar to the observation under hyperoxia stimulation. Moreover, we observed significantly reduced phosphorylation of focal adhesion kinase and increased permeability in MLE-12 cells treated with PLGF. These results suggest that PLGF triggers focal adhesion disassembly in alveolar type II cells via inhibiting the activation of focal adhesion kinase. Our findings reveal a novel role of PLGF in hyperoxia-induced lung injury and provide a potential target for the management of hyperoxia-induced acute lung injury.

Microarray analysis reveals the changes of circular RNA expression and molecular mechanism in acute lung injury mouse model

“…The mmu_circRNA_44122 and mmu_circRNA_44123 might act as a ceRNA to mediate PGF via sponging mmu‐mir‐7033‐5p (Figure B). Many studies have shown that PGF could promote the occurrence of ALI in the mouse and rat model . Previous research has shown that PGF can trigger the focal adhesion decomposition of type II alveolar cells by suppressing the expression of focal adhesion kinase and then induce the occurrence of ALI .…”

Risk factors for pulmonary arterial hypertension in children and young adults

“…The “new bronchopulmonary dysplasia” has recently been described as originating from a multifactorial etiology, including high tidal volumes during mechanical ventilation, leading to hyperoxic and barotrauma induced inflammation, patent ductus arteriosus with volume overload, maternal chorioamnionitis, and genetic factors . Growth factors involved in alverolarization, structure and function of the developing pulmonary circulation after preterm birth may play an important role in hyperoxia‐induced lung injury . The pulmonary vascular changes contribute to high pulmonary vascular resistance, with decreased angiogenesis and vascular surface area in a growing child .…”

Some neonatal risk factors for adult pulmonary arterial hypertension remain unknown

“…Pathomechanisms contributing to BPD are poorly understood. Genes upregulating during alveolarisation, followed by growth inhibitors, play an important role in the hyperoxia‐induced lung injury, as well as several other growth factors . We hypothesise that factors related to impaired lung growth among premature infants with cardiovascular malformations may have an impact on the development of adult PH.…”