Specific epigenetic regulators serve as potential therapeutic targets in idiopathic pulmonary fibrosis

• Published in: Heliyon Vol. 8; no. 8; p. e09773
• Main Authors: Sehgal, Manas, Jakhete, Sharayu Manish, Manekar, Amruta Ganesh, Sasikumar, Satish
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.08.2022; Elsevier
• Subjects: Epigenetics; Histone deacetylases; Pulmonary fibrosis; Review; Sirtuin; Smad; Transforming growth factor-β; Epigenetics; Smad; Pulmonary fibrosis; Histone deacetylases; Sirtuin; Transforming growth factor-β
• ISSN: 2405-8440; 2405-8440
• DOI: 10.1016/j.heliyon.2022.e09773

Idiopathic pulmonary fibrosis (IPF), a disorder observed mostly in older human beings, is characterised by chronic and progressive lung scarring leading to an irreversible decline in lung function. This health condition has a dismal prognosis and the currently available drugs only delay but fail to reverse the progression of lung damage. Consequently, it becomes imperative to discover improved therapeutic compounds and their cellular targets to cure IPF. In this regard, a number of recent studies have targeted the epigenetic regulation by histone deacetylases (HDACs) to develop and categorise antifibrotic drugs for lungs. Therefore, this review focuses on how aberrant expression or activity of Classes I, II and III HDACs alter TGF-β signalling to promote events such as epithelial-mesenchymal transition, differentiation of activated fibroblasts into myofibroblasts, and excess deposition of the extracellular matrix to propel lung fibrosis. Further, this study describes how certain chemical compounds or dietary changes modulate dysregulated HDACs to attenuate five faulty TGF-β-dependent profibrotic processes, both in animal models and cell lines replicating IPF, thereby identifying promising means to treat this lung disorder. [Display omitted] •IPF is promoted by aberrant levels or activity of histone deacetylases (HDACs).•Dysregulated HDACs modify TGF-β signalling in a fibrotic lung.•Certain drugs, which target faulty HDACs and TGF-β signals, mitigate lung fibrosis. Epigenetics; Histone deacetylases; Pulmonary fibrosis; Sirtuin; Smad; Transforming growth factor-β.