Placenta growth factor contributes to cell apoptosis and epithelial-to-mesenchymal transition in the hyperoxia-induced acute lung injury

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• 作者：Liang Zhang^a ; ^{lzhang@cmu.edu.cn" class="auth_mail" title="E-mail the corresponding author} ; Shuang Zhao^b ; Lijie Yuan^c ; Hongmin Wu^a ; Hong Jiang^d ; Gang Luo^d
• 关键词：PLGF ; Hyperoxia ; Lung injury ; Apoptosis ; EMT
• 刊名：Life Sciences
• 出版年：2016
• 出版时间：1 July 2016
• 年：2016
• 卷：156
• 期：Complete
• 页码：30-37
• 全文大小：2471 K

文摘

To investigate the role of placenta growth factor (PLGF) in hyperoxia-induced lung injury in preterm born rats.

Main methods

Primary alveolar epithelial cells type II (AECIIs) were exposed to 90% oxygen for 24 h. Preterm born rats were delivered by caesarean section, injected with PLGF-shRNA, and exposed to 90% oxygen for 14 days. MTT was used to examine the viability of cells. ELISA was used to measure the secretion of PLGF in primary AECIIs and bronchoalveolar lavage fluid. Flow cytometry and TUNEL staining were used to measure cell apoptosis in the lung. Expression of PLGF mRNA was detected using real-time PCR, and protein expression of PLGF and apoptotic proteins was detected using Western blotting analysis. Immunofluorescence staining was used to measure the expression of E-cadherin and α-smooth muscle actin (α-SMA).

Key findings

Exogenous PLGF inhibited viability of AECIIs. In addition, treatment of PLGF increased the percentage of apoptotic cells, regulated the expression of E-cadherin and α-SMA in the primary AECIIs. Moreover, PLGF exacerbated these pathological changes in hyperoxia-exposed AECIIs. In the in vivo study, shRNA mediated PLGF inhibition attenuated lung injury induced by hyperoxia exposure. In addition, PLGF inhibition reduced the percentage of apoptotic cells, increased the expression of Bcl-2 and decreased expression of Bax and cleaved-caspase 3. PLGF inhibition also reduced collagen deposition and inhibited epithelial-to-mesenchymal transition (EMT) in the lung of hyperoxia-exposed rat pups.

Significance

Our findings suggested that PLGF contributed to hyperoxia-induced lung injury through promoting apoptosis and EMT. PLGF may become a therapeutic target of hyperoxia-induced lung injury.