2020年2月
Increased expression of heme oxygenase-1 suppresses airway branching morphogenesis in fetal mouse lungs exposed to inflammation.
Pediatric research
- ,
- ,
- ,
- ,
- ,
- ,
- ,
- 巻
- 87
- 号
- 3
- 開始ページ
- 494
- 終了ページ
- 500
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1038/s41390-019-0588-0
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.
- リンク情報
- ID情報
-
- DOI : 10.1038/s41390-019-0588-0
- PubMed ID : 31578032