title: Placenta growth factor contributes to cell apoptosis and epithelial-to-mesenchymal transition in the hyperoxia-induced acute lung injury.
abstract: OBJECTIVE
  To investigate the role of placenta growth factor (PLGF) in hyperoxia-induced lung injury in preterm born rats.
  
  
  METHODS
  Primary alveolar epithelial cells type II (AECIIs) were exposed to 90% oxygen for 24h. Preterm born rats were delivered by caesarean section, injected with PLGF-shRNA, and exposed to 90% oxygen for 14days. 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).
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Neonatology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, People's Republic of China. Electronic address: lzhang@cmu.edu.cn.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Pediatrics, Shenyang Fourth People's Hospital, Shenyang, Liaoning 110003, People's Republic of China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Department of Biochemistry and Molecular Biology, Harbin Medical University (Daqing Campus), Daqing, Heilongjiang 163319, People's Republic of China.
authors.forename: Lijie
authors.initials: L
authors.lastname: Yuan
authors.affiliation: Department of Neonatology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, People's Republic of China.
authors.forename: Hongmin
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Pediatrics, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, People's Republic of China.
authors.forename: Hong
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Department of Pediatrics, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, People's Republic of China.
authors.forename: Gang
authors.initials: G
authors.lastname: Luo
mesh_terms: D055371:Acute Lung Injury / Q000209:etiology* / Q000473:pathology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005260:Female; D018496:Hyperoxia / Q000150:complications*; D008297:Male; D000072483:Placenta Growth Factor / Q000494:pharmacology*; D047928:Premature Birth / Q000473:pathology; D011658:Pulmonary Fibrosis / Q000473:pathology; D034741:RNA, Small Interfering / Q000378:metabolism; D017207:Rats, Sprague-Dawley
chemical_list: D034741:RNA, Small Interfering; D000072483:Placenta Growth Factor
keywords: Apoptosis; EMT; Hyperoxia; Lung injury; PLGF