Urotensin upregulates transforming growth factor-β1 expression of asthma airway through ERK-dependent pathway

被引:22
作者
Zhang, Wei-xi [1 ,2 ]
Liang, Ya-feng [1 ,2 ]
Wang, Xiao-ming [1 ,2 ]
Nie, Ying [1 ,2 ]
Chong, Lei [1 ,2 ]
Lin, Li [1 ,2 ]
Chen, Chun [1 ,2 ]
Li, Chang-chong [1 ,2 ]
机构
[1] Wenzhou Med Coll, Dept Pediat Pulmonol, Affiliated Hosp 2, Wenzhou 325027, Zhejiang, Peoples R China
[2] Wenzhou Med Coll, Yuying Childrens Hosp, Wenzhou 325027, Zhejiang, Peoples R China
基金
中国国家自然科学基金;
关键词
Asthma; Urotensin II; Extracellular signal-regulated kinase; Transforming growth factor; Airway; SMOOTH-MUSCLE-CELLS; GROWTH-FACTOR-BETA; MAP KINASES; PROLIFERATION; INVOLVEMENT; ACTIVATION; MECHANISMS; RESPONSES; RECEPTOR;
D O I
10.1007/s11010-012-1229-7
中图分类号
Q2 [细胞生物学];
学科分类号
071013 [干细胞生物学];
摘要
Airway smooth muscle cells (ASMCs) play a key role in the process of asthma airway remodeling. Urotensin II (UII) and transforming growth factor (TGF)-beta are potent mitogens for ASMCs proliferation. The study was aimed to determine whether UII-upregulated TGF-beta-mediated ASMCs proliferation and extracellular signal-regulated kinase (ERK) was required for such an effect. OVA-sensitized rats were challenged to induce asthma. Lung morphology and airway dynamic parameters were monitored. ASMCs from control and asthma rats were purified for the measurement of UII and TGF-beta 1 expression. In vitro experiments were conducted to determine the direct effect of UII on TGF-beta 1 expression by ASMCs. Finally, U0126, an ERK inhibitor was used to examine the role of ERK pathway in UII mediated TGF-beta 1 upregulation. We found that both UII and TGF-beta 1 were upregulated in asthma lung tissues. In vitro study on ASMCs further revealed that UII may render its effect on ASMCs cells through the upregulation of TGF-beta 1. Data also supported the conclusion that ERK pathway was required, but not sufficient in UII-induced TGF-beta 1 upregulation. The current study provides new evidence that UII is involved in the TGF-beta mediated mitogenic effect on ASMCs. UII, at least partially, uses ERK pathway to render such effect.
引用
收藏
页码:291 / 298
页数:8
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