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

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Abstract

Airway smooth muscle cells (ASMCs) play a key role in the process of asthma airway remodeling. Urotensin II (UII) and transforming growth factor (TGF)-β are potent mitogens for ASMCs proliferation. The study was aimed to determine whether UII-upregulated TGF-β-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-β1 expression. In vitro experiments were conducted to determine the direct effect of UII on TGF-β1 expression by ASMCs. Finally, U0126, an ERK inhibitor was used to examine the role of ERK pathway in UII mediated TGF-β1 upregulation. We found that both UII and TGF-β1 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-β1. Data also supported the conclusion that ERK pathway was required, but not sufficient in UII-induced TGF-β1 upregulation. The current study provides new evidence that UII is involved in the TGF-β mediated mitogenic effect on ASMCs. UII, at least partially, uses ERK pathway to render such effect.

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Acknowledgments

This study was supported by grants from the National Natural Science Foundation of China (No:8100015 and No:30571981), the Provincial Natural Science Foundation of Zhejiang (No:2090327),and by Scientific Research Fund of Zhejiang Provincial Education Department (No:20070906).

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Authors and Affiliations

  1. Department of Pediatric Pulmonology, The Second Affiliated Hospital & Yuying Children’s Hospital, Wenzhou Medical College, Wenzhou, 325027, Zhejiang, China

    Wei-xi Zhang, Ya-feng Liang, Xiao-ming Wang, Ying Nie, Lei Chong, Li Lin, Chun Chen & Chang-chong Li

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  1. Wei-xi Zhang
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  2. Ya-feng Liang
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  3. Xiao-ming Wang
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  4. Ying Nie
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  5. Lei Chong
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  6. Li Lin
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  7. Chun Chen
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  8. Chang-chong Li
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Correspondence to Chang-chong Li.

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W. Zhang and Y. Liang have contributed equally to this study.

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Zhang, Wx., Liang, Yf., Wang, Xm. et al. Urotensin upregulates transforming growth factor-β1 expression of asthma airway through ERK-dependent pathway. Mol Cell Biochem 364, 291–298 (2012). https://doi.org/10.1007/s11010-012-1229-7

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  • DOI: https://doi.org/10.1007/s11010-012-1229-7

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