Histone Acetylation and Modifiers in Renal Fibrosis

Abstract

Histones are the most abundant proteins bound to DNA in eukaryotic cells and frequently subjected to post-modifications such as acetylation, methylation, phosphorylation and ubiquitination. Many studies have shown that histone modifications, especially histone acetylation, play an important role in the development and progression of renal fibrosis. Histone acetylation is regulated by three families of proteins, including histone acetyltransferases (HATs), histone deacetylases (HDACs) and bromodomain and extraterminal (BET) proteins. These acetylation modifiers are involved in a variety of pathophysiological processes leading to the development of renal fibrosis, including partial epithelial-mesenchymal transition, renal fibroblast activation, inflammatory response, and the expression of pro-fibrosis factors. In this review, we summarize the role and regulatory mechanisms of HATs, HDACs and BET proteins in renal fibrosis and provide evidence for targeting these modifiers to treat various chronic fibrotic kidney diseases in animal models.

Therapeutic effects of selective p300 histone acetyl-transferase inhibitor on liver fibrosis

“…Liver fibrosis pathogenesis can be initiated by many diseases, but current studies aim to elucidate the underlying molecular mechanisms. Recent efforts have focused on the regulation of histone acetylation by HATs and HDACs in the progression of fibrotic disease ( 32 , 33 ). Normally, the HAT enzyme p300 activates gene transcription by inducing acetylation of histone tails ( 19 ).…”

Epigenetic modification in liver fibrosis: Promising therapeutic direction with significant challenges ahead

“…HATs, which catalyze histone acetylation, can be divided into three categories: p300/CBP, Gcn5-related N -acetyltransferases (GNATs) superfamily and MYST proteins 58 . P300/CBP proteins could stimulate histones acetylation at the enhancer and promoter regions of target genes and act as a transcription coactivator by cooperating with several transcription factors, including NF- κ B, AP1 and STAT.…”

Long non-coding RNAs: key regulators of liver and kidney fibrogenesis

“…Myofibroblasts are derived from various sources, including resident fibroblasts, pericytes, and epithelial cells that undergo a process of epithelial-to-mesenchymal transition (EMT). The production and deposition of excess ECM proteins by myofibroblasts lead to the formation of scar tissue, which can impair kidney function ( 33 - 38 ). Although drivers of liver/kidney damage might affect organs in an organ-specific manner, the fibrogenesis and associated cascades are conserved between organs ( 39 ).…”