| First Author | Arai Y | Year | 2020 |
| Journal | Pediatr Res | Volume | 87 |
| Issue | 3 | Pages | 494-500 |
| PubMed ID | 31578032 | Mgi Jnum | J:303634 |
| Mgi Id | MGI:6690774 | Doi | 10.1038/s41390-019-0588-0 |
| Citation | Arai Y, et al. (2020) Increased expression of heme oxygenase-1 suppresses airway branching morphogenesis in fetal mouse lungs exposed to inflammation. Pediatr Res 87(3):494-500 |
| abstractText | BACKGROUND: Intrauterine inflammation affects fetal lung development. BTB and CNC homology 1 (Bach1) is a transcriptional repressor of heme oxygenase-1 (HO-1) and interleukin-6 (IL-6) genes. We investigated the role of Bach1 in the development of fetal mouse lungs exposed to lipopolysaccharide (LPS) using a whole fetal lung tissue culture system. METHODS: We isolated and cultured embryonic day 12.5 fetal mouse lungs from pregnant Bach1 knockout ((-/-)) and wild-type (WT) mice. Airway branching morphogenesis was assessed by microscopically counting peripheral lung buds after incubation with/without LPS. Expression levels of genes related to inflammation and oxidative stress were evaluated using quantitative PCR. Zinc protoporphyrin, HO-1-specific inhibitor, was used. RESULTS: Branching morphogenesis was observed in Bach1(-/-) and WT fetal mice lungs without LPS exposure; after exposure to LPS, the number of peripheral lung buds was suppressed in Bach1(-/-) group only. Basal messenger RNA (mRNA) and protein expression of HO-1 was significantly higher in Bach1(-/-) group than in WT group; IL-6 and monocyte chemoattractant protein-1 mRNA expression was significantly increased after LPS exposure in both groups. Zinc protoporphyrin mitigated the LPS-induced suppression of branching morphogenesis in Bach1(-/-) mice. CONCLUSION: The ablation of Bach1 suppresses airway branching morphogenesis after LPS exposure by increased basal expression levels of HO-1. |
