EZH2 serves as a promising therapeutic target for fibrosis

Bioorg Chem. 2023 Aug:137:106578. doi: 10.1016/j.bioorg.2023.106578. Epub 2023 May 3.

Abstract

Fibrosis affects the function of many organs and tissues, and its persistent development can lead to tissue sclerosis and cancer, even leading to death further. Recent studies suggested that enhancer of zeste homolog 2 (EZH2), a major regulator of epigenetic repression, played an important role in the occurrence and development of fibrosis through gene silencing or transcriptional activation. As the most studied and powerful pro-fibrotic cytokine closely related to EZH2, TGF-β1 was primarily involved in the regulation of fibrosis along with the typical Smads and non-Smads signaling pathways. In addition, EZH2 inhibitors demonstrated inhibitory effects in several types of fibrosis. This review summarized the relationship underlying the action of EZH2, TGF-β1/Smads, and TGF-β1/non-Smads with fibrosis and described the research progress of EZH2 inhibitors in the treatment of fibrosis.

Keywords: EZH2; Fibrosis; Inhibitors; Smads; TGF-β1.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Enhancer of Zeste Homolog 2 Protein* / genetics
  • Enhancer of Zeste Homolog 2 Protein* / metabolism
  • Fibrosis
  • Humans
  • Signal Transduction
  • Transcriptional Activation
  • Transforming Growth Factor beta1* / metabolism

Substances

  • Transforming Growth Factor beta1
  • Enhancer of Zeste Homolog 2 Protein
  • EZH2 protein, human