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Sirtuins as novel pharmacological targets in podocyte injury and related glomerular diseases. | LitMetric

Sirtuins as novel pharmacological targets in podocyte injury and related glomerular diseases.

Biomed Pharmacother

Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China. Electronic address:

Published: November 2022

AI Article Synopsis

  • - Podocyte injury is a key factor in kidney disease leading to proteinuria and rapid disease progression; sirtuins are important proteins that help protect podocytes by promoting repair and regulating various cellular processes.
  • - Sirtuins play a protective role against glomerular diseases related to podocyte injury by improving immune response, reducing oxidative stress, maintaining cellular functions, and regulating metabolism; their deficiency is linked to podocyte damage.
  • - Research shows that activating sirtuins can have protective effects in various kidney diseases, indicating that targeting sirtuins could be a promising strategy for treating conditions related to podocyte injury.

Article Abstract

Podocyte injury is a major cause of proteinuria in kidney diseases, and persistent loss of podocytes leads to rapid irreversible progression of kidney disease. Sirtuins, a class of nicotinamide adenine dinucleotide-dependent deacetylases, can promote DNA repair, modify transcription factors, and regulate the cell cycle. Additionally, sirtuins play a critical role in renoprotection, particularly against podocyte injury. They also have pleiotropic protective effects on podocyte injury-related glomerular diseases, such as improving the immune inflammatory status and oxidative stress levels, maintaining mitochondrial homeostasis, enhancing autophagy, and regulating lipid metabolism. Sirtuins deficiency causes podocyte injury in different glomerular diseases. Studies using podocyte sirtuin-specific knockout and transgenic models corroborate this conclusion. Of note, sirtuin activators have protective effects in different podocyte injury-related glomerular diseases, including diabetic kidney disease, focal segmental glomerulosclerosis, membranous nephropathy, IgA nephropathy, and lupus nephritis. These findings suggest that sirtuins are promising therapeutic targets for preventing podocyte injury. This review provides an overview of recent advances in the role of sirtuins in kidney diseases, especially their role in podocyte injury, and summarizes the possible rationale for sirtuins as targets for pharmacological intervention in podocyte injury-related glomerular diseases.

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Source
http://dx.doi.org/10.1016/j.biopha.2022.113620DOI Listing

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