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Klotho suppresses RIG-I-mediated senescence-associated inflammation

Nature Cell Biology volume 13, pages 254–262 (2011)Cite this article

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An Erratum to this article was published on 01 April 2011

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Abstract

It is well known that aged or senescent cells develop a complex senescence-associated secretory phenotype (SASP), which is observed both in culture and in vivo. However, the mechanisms underlying the induction of the SASP are largely unknown. We demonstrate that retinoic-acid-inducible gene-I (RIG-I) is induced through the ataxia telangiectasia mutated–interferon regulatory factor 1 (ATM–IRF1) axis in senescent cells and that RIG-I signalling mediates the expression of two important mediators of inflammation, interleukin-6 (IL-6) and IL-8. Klotho has been associated with ageing. We show here that the intracellular, but not the secreted, form of klotho interacts with RIG-I and that this interaction inhibits RIG-I-induced expression of IL-6 and IL-8 both in vitro and in vivo. Our study uncovers a mechanism in which klotho functions as an anti-ageing factor through the suppression of RIG-I-mediated inflammation.

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Figure 1: Correlation of induction of RIG-I with interleukins, and reduction of klotho in replicative senescent cells.
Figure 2: RIG-I signalling mediates senescence-associated inflammation.
Figure 3: Endogenous klotho is a physiological inhibitor of RIG-I-mediated expression of IL-6.
Figure 4: Klotho inhibits RIG-I-mediated activation of NF-κB.
Figure 5: RIG-I-mediated expression of IL-6 and 8 is suppressed by intracellular, not secreted, klotho.
Figure 6: Inhibition of RIG-I-mediated expression of interleukins by klotho through the block of RIG-I multimerization.

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Change history

  • 16 March 2011

    In the version of this article initially published online, a graph in Fig. 3b was mislabelled and there were errors in the text on pages 4 and 5 and in the figure legend for Fig. 4c.

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Acknowledgements

We thank H. Shu, C. R. Abraham, M. Kuro-o, R. T. Moon and Y. Yang for plasmids, H. Deng and Y. Gao for irradiation, J. Luo and T. Tong for cell lines, Z. J. Chen and M. Kuro-o for knockout mice, M. Kuro-o for comments and J. L. Teeling for revising this paper. This work was supported by grants (2010CB911801 and 2011CB503904) from the National Basic Research Program, China.

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Author notes

  1. Feng Liu and Su Wu: These authors contributed equally to this work

  2. Jun Gu is a Present address: Department of Biochemistry and Molecular Biology, College of Life Sciences, Peking University, Beijing 100871, China

  3. Correspondence should be addressed to J.G. (e-mail: gj@pku.edu.cn)

Authors and Affiliations

  1. National Key Laboratory of Protein Engineering and Plant Gene Engineering, LSC, Peking University, Beijing 100871, China

    Feng Liu, Su Wu, Hongwei Ren & Jun Gu

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  1. Feng Liu
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F.L. and S.W. designed and conducted experiments, analysed the data and wrote the manuscript. H.R. carried out experiments. J.G. designed experiments and analysed the data, and wrote the manuscript.

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Correspondence to Jun Gu.

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Liu, F., Wu, S., Ren, H. et al. Klotho suppresses RIG-I-mediated senescence-associated inflammation. Nat Cell Biol 13, 254–262 (2011). https://doi.org/10.1038/ncb2167

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