EZH2 serves as a promising therapeutic target for fibrosis

Qian Zhang; Ya-Xi Wu; Xiao-Qian Yu; Bao-Yin Zhang; Li-Ying Ma

doi:10.1016/j.bioorg.2023.106578

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.

Authors

Qian Zhang¹, Ya-Xi Wu¹, Xiao-Qian Yu¹, Bao-Yin Zhang², Li-Ying Ma³

Affiliations

¹ State Key Laboratory of Esophageal Cancer Prevention and Treatment, Key Laboratory of Advanced Pharmaceutical Technology, Ministry of Education of China, School of Pharmaceutical Science and Institute of Pharmaceutical Science, Zhengzhou University, Zhengzhou, Henan 450001, PR China.
² Department of Pharmacy, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, PR China. Electronic address: baoyin05@126.com.
³ State Key Laboratory of Esophageal Cancer Prevention and Treatment, Key Laboratory of Advanced Pharmaceutical Technology, Ministry of Education of China, School of Pharmaceutical Science and Institute of Pharmaceutical Science, Zhengzhou University, Zhengzhou, Henan 450001, PR China; China Meheco Topfond Pharmaceutical Co., Key Laboratory of Cardio-cerebrovascular Drug, Zhumadian 463000, PR China. Electronic address: maliying@zzu.edu.cn.

PMID: 37156135
DOI: 10.1016/j.bioorg.2023.106578

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