Increased expression of CHOP and LC3B in newborn rats with bronchopulmonary dysplasia

Bronchopulmonary dysplasia (BPD) seriously affects the health and prognosis of children, but the efficacy of treatments is poor. The present study aimed to examine the effects of C/EBP homologous protein (CHOP), activating transcription factor 4 (ATF4) and microtubule-associated protein light chain 3 (LC3B), and the interaction between CHOP and LC3B, in newborn rats with BPD. At 1, 7, 14 and 21 days, the rats in the model [fraction of inspired oxygen (FiO(2))=80-85%] and control groups (FiO(2)=21%) were randomly sacrificed, and lung samples were collected. Alveolar development was evaluated according to the radial alveolar count (RAC) and alveolar septum thickness. Ultrastructural changes were observed by transmission electron microscopy (TEM), the expression levels of CHOP, ATF4 and LC3B were determined by immunohistochemistry, and western blot and reverse transcription-quantitative polymerase chain reaction analyses. The co-localization of CHOP and LC3B in lung tissues was determined by immunofluorescence. The results showed that, compared with the control group, alveolarization arrest was present in the model group. The TEM observations revealed that, at 14 days, type II alveolar epithelial cell (AECII) lamellar bodies were damaged, with an apparent dilation of the endoplasmic reticulum (ER) and autophagy in cells within the model group. Between days 7 and 14, the protein levels of ATF4, CHOP and LC3B were significantly increased in the model group. The mRNA levels of CHOP and LC3B were lower at days 7-21. CHOP and LC3B were co-localized in the cells of the lung tissues at day 14 in the model group. Pearson's correlation analysis showed that the protein levels of CHOP and LC3B-II were positively correlated in the model groups. As in previous studies, the present study demonstrated that BPD damaged the AECII cells, which exhibited detached and sparse microvilli and the vacuolization of lamellar bodies. In addition, it was found that the ER was dilated, with autophagosomes containing ER and other organelles in AECII cells; the expression levels of CHOP and LC3B-II were upregulated. CHOP and LC3B-II may have joint involvement in the occurrence and development of BPD.