HDAC inhibitors in experimental liver and kidney fibrosis

Abstract

Histone deacetylase (HDAC) inhibitors have been extensively studied in experimental models of cancer, where their inhibition of deacetylation has been proven to regulate cell survival, proliferation, differentiation and apoptosis. This in turn has led to the use of a variety of HDAC inhibitors in clinical trials. In recent years the applicability of HDAC inhibitors in other areas of disease has been explored, including the treatment of fibrotic disorders. Impaired wound healing involves the continuous deposition and cross-linking of extracellular matrix governed by myofibroblasts leading to diseases such as liver and kidney fibrosis; both diseases have high unmet medical needs which are a burden on health budgets worldwide. We provide an overview of the potential use of HDAC inhibitors against liver and kidney fibrosis using the current understanding of these inhibitors in experimental animal models and in vitro models of fibrosis.

Understanding the Epigenetic Syntax for the Genetic Alphabet in the Kidney

“…HDAC inhibitors were beneficial for the treatment of experimental FSGS and HIV-associated renal disease. 43 Although these are interesting initial observations, the concern is that both HDAC and DNMT inhibitors have pleotropic effects and they likely modify thousands of cytosines and histone tails. Further drug development to enhance specificity will likely be needed before potential human trials.…”

Embryonic Life of Hdac Inhibitors: – In Diabetic Nephropathy

“…[40] HDAC 2 PLAYS IMPORTANT ROLE IN DN [10] Among the six HDACs tested (HDAC-1 through -5 and HDAC-8), HDAC-2 activity significantly amplified in the kidneys of STZ-induced diabetic rats and db/db mice and TGF-β1-treated NRK52-E cells.…”

“…[12] NEPHROPATHY AND FIBROSIS [13,40] HDAC activity is also linked with the development and progression of some chronic diseases characterized by fibrosis, including chronic kidney disease, cardiac hypertrophy, and idiopathic pulmonary fibrosis. [13] www.wjpps.com Vol 6, Issue 9, 2017.…”

Activation of Sirtuin-1 Promotes Renal Fibroblast Activation and Aggravates Renal Fibrogenesis

“…Among the four classes of HDACs, class I and II HDACs have been extensively studied for their role in tissue fibrogenesis (Pang et al, 2009. It is evident that small molecular inhibitors acting on these two classes of HDACs were effective in attenuating fibrosis in multiple organs including kidney (Pang et al, 2009;Liu et al, 2013;Van Beneden et al, 2013). Apart from class I and II HDACs, the role of sirtuins (SIRTs), a class III HDAC, has also been intensively studied in animal models of kidney diseases.…”

“…Epigenetic modifications, such as acetylation/deacetylation, have also been linked to the pathogenesis of chronic kidney disease Van Beneden et al, 2013;Tampe and Zeisberg, 2014). Protein acetylation is regulated by a network of enzyme systems, namely, histone acetyltransferases and histone deacetylases (HDACs).…”