Increased expression of heme oxygenase-1 suppresses airway branching morphogenesis in fetal mouse lungs exposed to inflammation

Yukio Arai, Masato Ito, Kosuke Tanaka, Junichi Ozawa, Yukiko Motojima, Kikumi Matsuoka, Kazuhiko Igarashi, Fumihiko Namba

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)494-500
Number of pages7
JournalPediatric Research
Volume87
Issue number3
DOIs
Publication statusPublished - 2020 Feb 1
Externally publishedYes

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Fingerprint

Dive into the research topics of 'Increased expression of heme oxygenase-1 suppresses airway branching morphogenesis in fetal mouse lungs exposed to inflammation'. Together they form a unique fingerprint.

Cite this