title: Angiotensin-(1-7) attenuates lung fibrosis by way of Mas receptor in acute lung injury.
abstract: BACKGROUND
  Pulmonary fibrosis occurs in approximately 60% of patients with acute respiratory distress syndrome and has been significantly correlated with a poor outcome. The overexpression of angiotensin (Ang) II can induce lung inflammation and fibrosis. This observation, coupled with the knowledge that Ang-(1-7) is considered to be an endogenous antagonist of Ang II, led us to hypothesize that Ang-(1-7) would prevent lung remodeling in patients with acute respiratory distress syndrome.
  
  
  METHODS
  The protocol involved five groups: (1) control, (2) lipopolysaccharide (LPS), (3) losartan as a positive control group, (4) Ang-(1-7), and (5) [D-Ala7]-Ang-(1-7) (A779), an antagonist of the Ang-(1-7) receptor. Acute lung injury was induced by an intratracheal injection of LPS 5 mg/kg in C57BL/6 mice. Losartan (10 mg/kg) was administered by gavage daily, starting from 1 d before LPS stimulation. Ang-(1-7) or A779 in saline (100 ng/kg/min) was infused subcutaneously 1 h before acute lung injury induction for 3 or 7 d. The lung tissues were harvested for analysis at day 3 or 7 after injection of LPS.
  
  
  RESULTS
  LPS stimulation resulted in significantly increased inflammation, edema, and lung collagen production. With Ang-(1-7) treatment, the lung fibrosis score and hydroxyproline level were significantly reduced, and the expression of transforming growth factor-β and Smad2/3 were decreased on days 3 and 7. Losartan attenuated lung fibrosis similarly to Ang-(1-7) after LPS exposure. In the A779 group, a tendency was seen to aggravate collagen deposition and lung remodeling.
  
  
  CONCLUSIONS
  These findings indicate an antiremodeling role for Ang-(1-7) in acute lung injury, similar to the blocker of Ang II receptor, that might be at least partially mediated through an Ang-(1-7) receptor.
authors.affiliation: Department of Critical Care Medicine, Nanjing Zhong-Da Hospital, Southeast University School of Medicine, Nanjing, People's Republic of China.
authors.forename: Qiuhua
authors.initials: Q
authors.lastname: Chen
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
authors.forename: Yingzi
authors.initials: Y
authors.lastname: Huang
authors.forename: Chun
authors.initials: C
authors.lastname: Pan
authors.forename: Ling
authors.initials: L
authors.lastname: Liu
authors.forename: Haibo
authors.initials: H
authors.lastname: Qiu
mesh_terms: D055371:Acute Lung Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000803:Angiotensin I / Q000378:metabolism / Q000494:pharmacology*; D000804:Angiotensin II / Q000378:metabolism; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D004195:Disease Models, Animal; D008070:Lipopolysaccharides / Q000494:pharmacology; D019808:Losartan / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011658:Pulmonary Fibrosis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012128:Respiratory Distress Syndrome / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D014665:Vasodilator Agents / Q000378:metabolism / Q000494:pharmacology
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D008070:Lipopolysaccharides; D010446:Peptide Fragments; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D043562:Receptors, G-Protein-Coupled; D014665:Vasodilator Agents; D000804:Angiotensin II; D000803:Angiotensin I; C118790:angiotensin I (1-7); D019808:Losartan
keywords: Acute lung injury; Acute respiratory distress syndrome; Angiotensin II; Angiotensin-(1-7); Fibrosis; Mas receptor