Abstract |
The roles of epigenetic modulation of gene expression and protein functions in autosomal dominant polycystic kidney disease ( ADPKD) have recently become the focus of scientific investigation. Evidence generated to date indicates that one of the epigenetic modifiers, histone deacetylases (HDACs), are important regulators of ADPKD. HDACs are involved in regulating the expression of the Pkd1 gene and are the target of fluid flow-induced calcium signal in kidney epithelial cells. Pharmacological inhibition of HDAC activity has been found to reduce the progression of cyst formation and slow the decline of kidney function in Pkd1 conditional knockout mice and Pkd2 knockout mice, respectively, implicating the potential clinical application of HDAC inhibitors on ADPKD. Since the expression of HDAC6 is upregulated in cystic epithelial cells, the potential roles of HDAC6 in regulating cilia resorption and epidermal growth factor receptor (EGFR) trafficking through deacetylating α- tubulin and regulating Wnt signaling through deacetylating β- catenin are also discussed. This article is part of a Special Issue entitled: Polycystic Kidney Disease.
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Authors | Xiaogang Li |
Journal | Biochimica et biophysica acta
(Biochim Biophys Acta)
Vol. 1812
Issue 10
Pg. 1213-8
(Oct 2011)
ISSN: 0006-3002 [Print] Netherlands |
PMID | 20970496
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review)
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Copyright | Copyright © 2010 Elsevier B.V. All rights reserved. |
Chemical References |
- Histone Deacetylase Inhibitors
- TRPP Cation Channels
- polycystic kidney disease 1 protein
- polycystic kidney disease 2 protein
- Histone Deacetylases
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Topics |
- Animals
- Disease Models, Animal
- Epigenesis, Genetic
- Histone Deacetylase Inhibitors
(pharmacology)
- Histone Deacetylases
(classification, genetics, metabolism)
- Humans
- Mice
- Models, Biological
- Polycystic Kidney, Autosomal Dominant
(drug therapy, etiology, genetics, metabolism)
- Signal Transduction
- TRPP Cation Channels
(genetics)
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