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 language | English |
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Pages (from-to) | 47-54 |
Number of pages | 8 |
Journal | Neonatology |
Volume | 101 |
Issue number | 1 |
DOIs | |
Publication status | Published - Dec 2011 |
Keywords
- Bronchopulmonary dysplasia
- Collagen
- Hyperoxia
- Renin-angiotensin system
ASJC Scopus subject areas
- Pediatrics, Perinatology, and Child Health
- Developmental Biology