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Histone deacetylase 3 (HDAC3) as an important epigenetic regulator of kidney diseases

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Abstract

Development and progression of many kidney diseases are substantially influenced by aberrant protein acetylation modifications of gene expression crucial for kidney functions. Histone deacetylase (HDAC) expression alterations are detected from renal samples of patients and animal models of various kidney diseases, and the administrations of HDAC inhibitors display impressive renal protective effects in vitro and in vivo. However, when the expression alterations of multiple HDACs occur, not all the HDACs causally affect the disease onset or progression. Identification of a single HDAC as a disease-causing factor will allow subtype-targeted intervention with less side effect. HDAC3 is a unique HDAC with distinct structural and subcellular distribution features and co-repressor dependency. HDAC3 is required for kidney development and its aberrations actively participate in many pathological processes, such as cancer, cardiovascular diseases, diabetes, and neurodegenerative disorders, and contribute significantly to the pathogenesis of kidney diseases. This review will discuss the recent studies that investigate the critical roles of HDAC3 aberrations in kidney development, renal aging, renal cell carcinoma, renal fibrosis, chronic kidney disease, polycystic kidney disease, glomerular podocyte injury, and diabetic nephropathy. These studies reveal the distinct characters of HDAC3 aberrations that act on different molecules/signaling pathways under various renal pathological conditions, which might shed lights into the epigenetic mechanisms of renal diseases and the potentially therapeutic strategies.

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Acknowledgements

The authors thank formal and current lab members Dr. Lin Liu, Wenjun Lin, Jun Yang, and Fang Chen for their contributions to the publications cited in this article.

Funding

This study is supported by research grants from National Nature Science Foundation of China General Program 81970577 and 81670762.

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Authors and Affiliations

  1. Department of Nephrology, Northern Jiangsu People’s Hospital, Nanjing University School of Medicine, Yangzhou, 225001, China

    Lijun Zhang & Wangsen Cao

  2. Jiangsu Key Lab of Molecular Medicine, Nanjing University School of Medicine, Nanjing, 210093, China

    Lijun Zhang & Wangsen Cao

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  1. Lijun Zhang
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  2. Wangsen Cao
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Contributions

Conceptual design, WC; data mining and collection, LZ; manuscript preparation, LZ and WC; manuscript editing and writing, WC. Both authors approved the final version of the manuscript.

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Correspondence to Wangsen Cao.

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Zhang, L., Cao, W. Histone deacetylase 3 (HDAC3) as an important epigenetic regulator of kidney diseases. J Mol Med 100, 43–51 (2022). https://doi.org/10.1007/s00109-021-02141-8

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  • DOI: https://doi.org/10.1007/s00109-021-02141-8

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