TY - JOUR
T1 - The renin-angiotensin system mediates hyperoxia-induced collagen production in human lung fibroblasts
AU - Lang, Yaw Dong
AU - Hung, Chien-Lung
AU - Wu, Tzu Ying
AU - Wang, Leng-Fang
AU - Chen, Chung Ming
N1 - Funding Information:
This work was supported by a grant from Taipei Medical University Hospital (98TMU-TMUH-08).
PY - 2010/7
Y1 - 2010/7
N2 - 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.
AB - 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.
KW - Angiotensin II
KW - Angiotensin II type 1 receptor
KW - Angiotensin-converting enzyme
KW - Hyperoxia
KW - Lung fibroblasts
KW - α-Smooth muscle actin
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U2 - 10.1016/j.freeradbiomed.2010.03.022
DO - 10.1016/j.freeradbiomed.2010.03.022
M3 - Article
C2 - 20353822
AN - SCOPUS:77953028657
SN - 0891-5849
VL - 49
SP - 88
EP - 95
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
IS - 1
ER -