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Epigenetic modifications of Klotho expression in kidney diseases

期刊

JOURNAL OF MOLECULAR MEDICINE-JMM
卷 99, 期 5, 页码 581-592

出版社

SPRINGER HEIDELBERG
DOI: 10.1007/s00109-021-02044-8

关键词

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

资金

  1. National Nature Science Foundation of China General Program [81970577, 81670762]

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Studies show that epigenetic modifications affect the Klotho gene in renal diseases, impacting disease progression. Lowered Klotho levels worsen the condition, but beneficial changes can be made through epigenetic interventions.
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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