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The stress-related hormone norepinephrine induced upregulation of Nix, contributing to ECM protein expression

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Cell Stress and Chaperones Aims and scope

Abstract

Organ fibrosis has been viewed as a major medical problem that leads to progressive dysfunction of the organ and eventually the death of patients. Stress-related hormone norepinephrine (NE) has been reported to exert fibrogenic actions in the injured organ. Nix plays a critical role in pressure overload-induced cardiac remodeling and heart failure through mediating cardiomyocyte apoptosis. However, cardiac remodeling also includes fibrosis. Whether Nix is involved in stress-induced fibrosis remains unclear. The present study was designed to determine the role of Nix in NE-induced NIH/3T3 fibroblasts. The results showed that Nix was upregulated and closely associated with cell proliferation, collagen and fibronectin expression in NIH/3T3 fibroblasts following NE treatment. Overexpression of Nix promoted collagen and fibronectin expression, whereas the suppression of Nix resulted in a strong reduction in collagen and fibronectin expression. Moreover, the increases in collagen and fibronectin expression induced by NE were successively increased when Nix was overexpressed and reduced when Nix was inhibited. Furthermore, we demonstrated that the PKC activation is responsible for the upregulation of Nix induced by NE. Inhibition of Nix expression with α-adrenoceptor antagonist, β-adrenoceptor antagonist or PKC inhibitor attenuated NE-induced collagen and fibronectin expression. Our data revealed that Nix is a novel mediator of NE-induced fibrosis. Thus, it would provide a new insight into the development of effective preventative measures and therapies of tissue fibrosis.

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Acknowledgments

We would like to thank professors Gerald W. Dorn II for providing the Nix plasmid. This work was supported by funds from the National Natural Science Foundation of China (31071022).

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Authors and Affiliations

  1. Department of Stress Medicine, Beijing Institute of Basic Medical Sciences, No. 27 Taiping Road, Haidian District, Beijing, 100850, China

    Weili Liu, Xinxing Wang, Jingbo Gong, Zhusong Mei, Xiujie Gao, Yun Zhao, Jing Ma & Lingjia Qian

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  1. Weili Liu
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  2. Xinxing Wang
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  3. Jingbo Gong
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  8. Lingjia Qian
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Correspondence to Lingjia Qian.

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Liu, W., Wang, X., Gong, J. et al. The stress-related hormone norepinephrine induced upregulation of Nix, contributing to ECM protein expression. Cell Stress and Chaperones 19, 903–912 (2014). https://doi.org/10.1007/s12192-014-0515-6

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  • DOI: https://doi.org/10.1007/s12192-014-0515-6

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