Activation of the renin-angiotensin system in hyperoxia-induced lung fibrosis in neonatal rats

Jiunn Song Jiang, Yaw Dong Lang, Hsiu-Chu Chou, Chwen-Ming Shih, Meng Ying Wu, Chung-Ming Chen, Leng-Fang Wang

Research output: Contribution to journalArticlepeer-review

22 Citations (Scopus)

Abstract

Background: Oxygen toxicity plays an important role in lung injury and may lead to bronchopulmonary dysplasia. We previously demonstrated that hyperoxia activated the renin-angiotensin system (RAS) in cultured human fetal lung fibroblasts. Objective: To examine whether the upregulation of RAS components is associated with hyperoxia-induced lung fibrosis in neonatal Sprague-Dawley rats. Methods: Experimental rat pups were exposed to 1 week of >95% O 2 and a further 2 weeks of 60% O 2. Control pups were exposed to room air over the same periods. Lung tissues were taken for biochemical and histochemical assays on postnatal days 7 and 21. Results: Hyperoxia significantly increased total collagen content and the expression of type I collagen and alpha smooth muscle actin when compared to control rats. RAS components including angiotensinogen, angiotensin-converting enzyme, angiotensin II, and angiotensin II type 1 receptor were significantly upregulated by hyperoxia. The results also demonstrated that only the extracellular signal-regulated kinase (ERK) signaling pathway was activated by hyperoxia exposure. p38 mitogen-activated protein kinase and c-Jun N-terminal kinase were not activated. Conclusions: Local RAS activation is involved in the pathogenesis of hyperoxia-induced lung fibrosis in neonatal rats. ERK phosphorylation might mediate angiotensin II type 1 receptor activation.

Original languageEnglish
Pages (from-to)47-54
Number of pages8
JournalNeonatology
Volume101
Issue number1
DOIs
Publication statusPublished - Dec 2011

Keywords

  • Bronchopulmonary dysplasia
  • Collagen
  • Hyperoxia
  • Renin-angiotensin system

ASJC Scopus subject areas

  • Developmental Biology
  • Pediatrics, Perinatology, and Child Health

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