Epigenetic modifications of Klotho expression in kidney diseases

Abstract

Developments of many renal diseases are substantially influenced by epigenetic modifications of numerous genes, mainly mediated by DNA methylations, histone modifications, and microRNA interference; however, not all gene modifications causally affect the disease onset or progression. Klotho is a critical gene whose repressions in various pathological conditions reportedly involve epigenetic regulatory mechanisms. Klotho is almost unexceptionally repressed early after acute or chronic renal injuries and its levels inversely correlated with the disease progression and severity. Moreover, the strategies of Klotho derepression via epigenetic modulations beneficially change the pathological courses both in vitro and in vivo. Hence, Klotho is not only considered a biomarker of the renal disease but also a potential or even an ideal target of therapeutic epigenetic intervention. Here, we summarize and discuss studies that investigate the Klotho repression and intervention in renal diseases from an epigenetic point of view. These information might shed new sights into the effective therapeutic strategies to prevent and treat various renal disorders.

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Acknowledgments

We thank former and current laboratory members Lin Liu, Qin Zhang, Wenjun Lin, Shasha Yin, Dawei Cai, Fangfang Bi, Yanning Li, Fang Chen, Ai Wei, Qi Gao, Xiaobo Zhu, Xingren Chen, and Lijun Zhang for their contributions to the publications substantiating this article.

Funding

This work is supported by research grants from National Nature Science Foundation of China General Program 81970577 and 81670762 to W.C.

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J.X. searched the literatures drafted the manuscript. W.C. reviewed, edited, and wrote the manuscript.

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Correspondence to Wangsen Cao.

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Xia, J., Cao, W. Epigenetic modifications of Klotho expression in kidney diseases. J Mol Med (2021). https://doi.org/10.1007/s00109-021-02044-8

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Keywords

  • Klotho
  • Epigenetics
  • DNA methylation
  • Histone acetylation
  • miRNA interference
  • Kidney diseases