Histone deacetylase: a potential therapeutic target for fibrotic disorders

Abstract

Histone deacetylases (HDACs) are enzymes that balance the acetylation activities of histone acetyltransferases on chromatin remodeling and play essential roles in regulating gene transcription. In the past several years, the role of HDACs in cancer initiation and progression, as well as the therapeutic effects of HDAC inhibitors in various types of cancer, has been well studied. Recent studies indicated that HDAC activity is also associated with the development and progression of some chronic diseases characterized by fibrosis, including chronic kidney disease, cardiac hypertrophy, and idiopathic pulmonary fibrosis. Here, we review what is known about HDACs in the progression of tissue fibrosis and the potential applications of HDAC inhibitors in the treatment of disorders associated with fibroblast activation and proliferation.

Fig. 1.

HDAC inhibitors attenuate STAT3-mediated fibrosis. HDAC activity is required for STAT3 phosphorylation at tyrosine 705 and dimerization (activation). The dimerized STAT3 is translocated into the nucleus, where it regulates transcription of the target genes associated with development of tissue fibrosis, such as α-smooth muscle actin, fibronectin, and collagen I. HDAC inhibitors such as TSA can inhibit these actions of STAT3 and subsequently attenuate its effects in association of fibrosis.