The roles of histone deacetylases in kidney development and disease

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Abstract

Histone deacetylases (HDACs) are important epigenetic regulators that mediate deacetylation of both histone and non-histone proteins. HDACs, especially class I HDACs, are highly expressed in developing kidney and subject to developmental control. HDACs play an important role in kidney formation, especial nephron progenitor maintenance and differentiation. Several lines of evidence support the critical role of HDACs in the development and progression of various kidney diseases. HDAC inhibitors (HDACis) are very effective in the prevention and treatment of kidney diseases (including kidney cancer). A better understanting of the molecular mechanisms underlying the role(s) of HDACs in the pathogenesis and progression of renal disease are likely to be of great help in developing more effective and less toxic selective HDAC inhibitors and combinatorial therapeutics.

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Most cited references 65

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Erasers of histone acetylation: the histone deacetylase enzymes.

Edward Seto, Minoru Yoshida (2014)

Histone deacetylases (HDACs) are enzymes that catalyze the removal of acetyl functional groups from the lysine residues of both histone and nonhistone proteins. In humans, there are 18 HDAC enzymes that use either zinc- or NAD(+)-dependent mechanisms to deacetylate acetyl lysine substrates. Although removal of histone acetyl epigenetic modification by HDACs regulates chromatin structure and transcription, deacetylation of nonhistones controls diverse cellular processes. HDAC inhibitors are already known potential anticancer agents and show promise for the treatment of many diseases.

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The many roles of histone deacetylases in development and physiology: implications for disease and therapy.

Michael Haberland, Rusty Montgomery, Eric Olson (2009)

Histone deacetylases (HDACs) are part of a vast family of enzymes that have crucial roles in numerous biological processes, largely through their repressive influence on transcription. The expression of many HDAC isoforms in eukaryotic cells raises questions about their possible specificity or redundancy, and whether they control global or specific programmes of gene expression. Recent analyses of HDAC knockout mice have revealed highly specific functions of individual HDACs in development and disease. Mutant mice lacking individual HDACs are a powerful tool for defining the functions of HDACs in vivo and the molecular targets of HDAC inhibitors in disease.

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Six2 defines and regulates a multipotent self-renewing nephron progenitor population throughout mammalian kidney development.

Akio Kobayashi, M Todd Valerius, Joshua Mugford … (2008)

Nephrons, the basic functional units of the kidney, are generated repetitively during kidney organogenesis from a mesenchymal progenitor population. Which cells within this pool give rise to nephrons and how multiple nephron lineages form during this protracted developmental process are unclear. We demonstrate that the Six2-expressing cap mesenchyme represents a multipotent nephron progenitor population. Six2-expressing cells give rise to all cell types of the main body of the nephron during all stages of nephrogenesis. Pulse labeling of Six2-expressing nephron progenitors at the onset of kidney development suggests that the Six2-expressing population is maintained by self-renewal. Clonal analysis indicates that at least some Six2-expressing cells are multipotent, contributing to multiple domains of the nephron. Furthermore, Six2 functions cell autonomously to maintain a progenitor cell status, as cap mesenchyme cells lacking Six2 activity contribute to ectopic nephron tubules, a mechanism dependent on a Wnt9b inductive signal. Taken together, our observations suggest that Six2 activity cell-autonomously regulates a multipotent nephron progenitor population.

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Author and article information

Contributors

Hongbing Liu:

ORCID: http://orcid.org/0000-0002-3411-4597

hliu8@tulane.edu

Journal

Journal ID (nlm-ta): Clin Exp Nephrol

Journal ID (iso-abbrev): Clin Exp Nephrol

Title: Clinical and Experimental Nephrology

Publisher: Springer Singapore (Singapore )

ISSN (Print): 1342-1751

ISSN (Electronic): 1437-7799

Publication date (Electronic): 4 January 2021

Publication date PMC-release: 4 January 2021

Publication date (Print): 2021

Volume: 25

Issue: 3

Pages: 215-223

Affiliations

GRID grid.265219.b, ISNI 0000 0001 2217 8588, Department of Pediatrics and The Tulane Hypertension and Renal Center of Excellence, , Tulane University School of Medicine, ; SL-37, 1430 Tulane Avenue, New Orleans, LA 70112 USA

Author information

Hongbing Liu http://orcid.org/0000-0002-3411-4597

Article

Publisher ID: 1995

DOI: 10.1007/s10157-020-01995-5

PMC ID: 7925501

PubMed ID: 33398599

SO-VID: 907ba355-d735-40a3-a590-dc90465b0882

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 17 November 2019

Date accepted : 10 November 2020

Funding

Funded by: FundRef http://dx.doi.org/10.13039/100000968, American Heart Association;

Award ID: 17SDG33660072

Award Recipient : Hongbing Liu

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ScienceOpen disciplines: Nephrology

Keywords: histone deacetylases,histone deacetylase inhibitors,kidney disease,kidney cancer

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ScienceOpen disciplines: Nephrology

Keywords: histone deacetylases, histone deacetylase inhibitors, kidney disease, kidney cancer

The roles of histone deacetylases in kidney development and disease

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Karger: Nephrology

Most cited references 65

Erasers of histone acetylation: the histone deacetylase enzymes.

The many roles of histone deacetylases in development and physiology: implications for disease and therapy.

Six2 defines and regulates a multipotent self-renewing nephron progenitor population throughout mammalian kidney development.

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