Epigenetic Modifiers as Potential Therapeutic Targets in Diabetic Kidney Disease.

International Journal of Molecular Sciences
Julio M Martinez-MorenoAna B Sanz

Abstract

Diabetic kidney disease is one of the fastest growing causes of death worldwide. Epigenetic regulators control gene expression and are potential therapeutic targets. There is functional interventional evidence for a role of DNA methylation and the histone post-translational modifications-histone methylation, acetylation and crotonylation-in the pathogenesis of kidney disease, including diabetic kidney disease. Readers of epigenetic marks, such as bromodomain and extra terminal (BET) proteins, are also therapeutic targets. Thus, the BD2 selective BET inhibitor apabetalone was the first epigenetic regulator to undergo phase-3 clinical trials in diabetic kidney disease with an endpoint of kidney function. The direct therapeutic modulation of epigenetic features is possible through pharmacological modulators of the specific enzymes involved and through the therapeutic use of the required substrates. Of further interest is the characterization of potential indirect effects of nephroprotective drugs on epigenetic regulation. Thus, SGLT2 inhibitors increase the circulating and tissue levels of β-hydroxybutyrate, a molecule that generates a specific histone modification, β-hydroxybutyrylation, which has been associated with the benefic...Continue Reading

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Citations

Feb 2, 2021·Diabetes, Metabolic Syndrome and Obesity : Targets and Therapy·Heng-Cheng LuLi-Yu He
Feb 28, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Junying LuShu Nie
Apr 3, 2021·Molecular and Cellular Endocrinology·Elena Cantero-NavarroAlberto Ortiz
Jun 3, 2021·Wound Repair and Regeneration : Official Publication of the Wound Healing Society [and] the European Tissue Repair Society·Alberto ZulloWerner Klingler
Jun 19, 2021·Frontiers in Endocrinology·Karina Ramírez-AlarcónMiquel Martorell

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Methods Mentioned

BETA
acetylation
histone acetylation
deacylation

Clinical Trials Mentioned

NCT02586155
NCT03160430
NCT03228940
NCT03817749
NCT04194450
NCT04073927

Software Mentioned

BETonMACE

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