title: Hyperoxia stimulates the transdifferentiation of type II alveolar epithelial cells in newborn rats.
abstract: Supplemental oxygen treatment in preterm infants may cause bronchopulmonary dysplasia (BPD), which is characterized by alveolar simplification and vascular disorganization. Despite type II alveolar epithelial cell (AEC II) damage being reported previously, we found no decrease in the AEC II-specific marker, surfactant protein C (SP-C), in the BPD model in our previous study. We thus speculated that AEC II injury is not a unique mechanism of BPD-related pulmonary epithelial repair dysfunction and that abnormal transdifferentiation can exist. Newborn rats were randomly assigned to model (85% oxygen inhalation) and control groups (room air inhalation). Expressions of AEC I (aquaporin 5, T1α) and AEC II markers (SP-C, SP-B) were detected at three levels: 1) in intact lung tissue, 2) in AEC II isolated from rats in the two groups, and 3) in AEC II isolated from newborn rats, which were further cultured under either hyperoxic or normoxic conditions. In the model group, increased AEC I was observed at both the tissue and cell level, and markedly increased transdifferentiation was observed by immunofluorescent double staining. Transmission electron microscopy revealed morphological changes in alveolar epithelium such as damaged AECs, a fused air-blood barrier structure, and opened tight junctions in the model group. These findings indicate that transdifferentiation of AECs is not suppressed but rather is increased under hyperoxic treatment by compensation; however, such repair during injury cannot offset pulmonary epithelial air exchange and barrier dysfunction caused by structural damage to AECs.
authors: Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, China.
authors: Ana
authors: A
authors: Hou
authors: Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, China.
authors: Jianhua
authors: J
authors: Fu
authors: Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, China.
authors: Haiping
authors: H
authors: Yang
authors: Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, China.
authors: Yuting
authors: Y
authors: Zhu
authors: Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, China.
authors: Yuqing
authors: Y
authors: Pan
authors: Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, China.
authors: Shuyan
authors: S
authors: Xu
authors: Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, China xdxue1111@126.com.
authors: Xindong
authors: X
authors: Xue
mesh_terms: D000818:Animals; D017209:Apoptosis; D051402:Aquaporin 5 / Q000096:biosynthesis; D015824:Blood-Air Barrier; D001997:Bronchopulmonary Dysplasia / Q000209:etiology; D049109:Cell Proliferation; D054338:Cell Transdifferentiation / Q000502:physiology*; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000166:cytology*; D018496:Hyperoxia; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D010100:Oxygen / Q000008:administration & dosage / Q000494:pharmacology*; D010455:Peptides / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000166:cytology* / Q000378:metabolism; D037701:Pulmonary Surfactant-Associated Protein B / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D020545:Respiratory Mucosa / Q000166:cytology*; D000098853:Podoplanin
chemical_list: D051402:Aquaporin 5; D008562:Membrane Glycoproteins; D010100:Oxygen; D010455:Peptides; D037701:Pulmonary Surfactant-Associated Protein B; C496040:Aqp5 protein, rat; C092025:Pdpn protein, rat; D000098853:Podoplanin; C077063:Sftpc protein, rat
keywords: alveolar epithelial cells; bronchopulmonary dysplasia; hyperoxia; transdifferentiation