The renin-angiotensin system mediates hyperoxia-induced collagen production in human lung fibroblasts

Yaw Dong Lang, Chien-Lung Hung, Tzu Ying Wu, Leng-Fang Wang, Chung Ming Chen

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

A high concentration of oxygen can cause lung injury and lead to pulmonary fibrosis. Angiotensin (Ang) II induces human lung fibroblast proliferation and stimulates collagen synthesis. However, the role of the renin-angiotensin system (RAS) in the pathogenesis of hyperoxia-induced collagen production is unclear. The aims of this study were to investigate the effects of hyperoxia on the components of the RAS and collagen expression in human lung fibroblasts (MRC-5). Hyperoxia increased total collagen, collagen type I, and α-smooth muscle actin (α-SMA) mRNA and protein expression. RAS components and Ang II production were also significantly increased after hyperoxic exposure. Hyperoxia induced Ang II type 1 receptor (AT1R) expression but did not alter AT2R expression, furthermore, silencing of AT1R signaling with small interfering RNA suppressed hyperoxia-induced phosphorylated-ERK (p-ERK) 1/2, α-SMA, and collagen type I expression. Ang II increased p-ERK 1/2 and collagen type I expression, and these increases were inhibited by the AT1R inhibitor, losartan, but not by the AT2R inhibitor, PD123319 under both normoxic and hyperoxic conditions. These data suggest Ang II-mediated signaling transduction via AT1R is involved in hyperoxia-induced collagen synthesis in human lung fibroblasts.

Original languageEnglish
Pages (from-to)88-95
Number of pages8
JournalFree Radical Biology and Medicine
Volume49
Issue number1
DOIs
Publication statusPublished - Jul 2010

Fingerprint

Hyperoxia
Angiotensins
Fibroblasts
Renin-Angiotensin System
Renin
Collagen
Angiotensin II
Lung
Collagen Type I
Angiotensin Type 1 Receptor
Losartan
Pulmonary Fibrosis
Small Interfering RNA
Lung Injury
Muscle
Actins
Smooth Muscle
Oxygen
Messenger RNA
Proteins

Keywords

  • α-Smooth muscle actin
  • Angiotensin II
  • Angiotensin II type 1 receptor
  • Angiotensin-converting enzyme
  • Hyperoxia
  • Lung fibroblasts

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)
  • Medicine(all)

Cite this

The renin-angiotensin system mediates hyperoxia-induced collagen production in human lung fibroblasts. / Lang, Yaw Dong; Hung, Chien-Lung; Wu, Tzu Ying; Wang, Leng-Fang; Chen, Chung Ming.

In: Free Radical Biology and Medicine, Vol. 49, No. 1, 07.2010, p. 88-95.

Research output: Contribution to journalArticle

Lang, Yaw Dong ; Hung, Chien-Lung ; Wu, Tzu Ying ; Wang, Leng-Fang ; Chen, Chung Ming. / The renin-angiotensin system mediates hyperoxia-induced collagen production in human lung fibroblasts. In: Free Radical Biology and Medicine. 2010 ; Vol. 49, No. 1. pp. 88-95.
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