title: Activation of the renin-angiotensin system in hyperoxia-induced lung fibrosis in neonatal rats.
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.
authors.affiliation: Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan, ROC.
authors.forename: Jiunn-Song
authors.initials: JS
authors.lastname: Jiang
authors.forename: Yaw-Dong
authors.initials: YD
authors.lastname: Lang
authors.forename: Hsiu-Chu
authors.initials: HC
authors.lastname: Chou
authors.forename: Chwen-Ming
authors.initials: CM
authors.lastname: Shih
authors.forename: Meng-Ying
authors.initials: MY
authors.lastname: Wu
authors.forename: Chung-Ming
authors.initials: CM
authors.lastname: Chen
authors.forename: Leng-Fang
authors.initials: LF
authors.lastname: Wang
mesh_terms: D000804:Angiotensin II / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D015415:Biomarkers / Q000378:metabolism; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D018507:Gene Expression Regulation, Developmental; D018496:Hyperoxia / Q000139:chemically induced*; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000235:genetics; D010100:Oxygen / Q000009:adverse effects*; D011658:Pulmonary Fibrosis / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism; D044139:Receptor, Angiotensin, Type 2 / Q000235:genetics / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000502:physiology*
chemical_list: D015415:Biomarkers; D024042:Collagen Type I; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D000804:Angiotensin II; D010100:Oxygen