Effect of EZH2 on pulmonary artery smooth muscle cell migration in pulmonary hypertension

Mol Med Rep. 2021 Feb;23(2):129. doi: 10.3892/mmr.2020.11768. Epub 2020 Dec 14.

Abstract

Pulmonary hypertension (PH) is a life‑threatening disease that often involves vascular remodeling. Although pulmonary arterial smooth muscle cells (PASMCs) are the primary participants in vascular remodeling, their biological role is not entirely clear. The present study analyzed the role of enhancer of zeste homolog 2 (EZH2) in vascular remodeling of PH by investigating the behavior of PASMCs. The expression levels of EZH2 in PASMCs in chronic thromboembolic pulmonary hypertension (CTEPH), a type of PH, were detected. The role of EZH2 in PASMC migration was investigated by wound‑healing assay following overexpression and knockdown. Functional enrichment analysis of the whole‑genome expression profiles of PASMCs with EZH2 overexpression was performed using an mRNA Human Gene Expression Microarray. Quantitative (q)PCR was performed to confirm the results of the microarray. EZH2 expression levels increased in CTEPH cell models. The overexpression of EZH2 enhanced PASMC migration compared with control conditions. Functional enrichment analysis of the differentially expressed genes following EZH2 overexpression indicated a strong link between EZH2 and the immune inflammatory response and oxidoreductase activity in PASMCs. mRNA expression levels of superoxide dismutase 3 were verified by qPCR. The results suggested that EZH2 was involved in the migration of PASMCs in PH, and may serve as a potential target for the treatment of PH.

Keywords: enhancer of zeste homolog 2; hypoxic pulmonary arterial hypertension; chronic thromboembolic pulmonary hypertension; pulmonary artery smooth muscle cells; migration; functional enrichment analysis.

MeSH terms

  • Cell Line
  • Cell Movement / genetics
  • Enhancer of Zeste Homolog 2 Protein / biosynthesis*
  • Enhancer of Zeste Homolog 2 Protein / genetics*
  • Female
  • Gene Expression Regulation
  • Gene Knockdown Techniques
  • Gene Ontology
  • Humans
  • Hypertension, Pulmonary / chemically induced
  • Hypertension, Pulmonary / genetics*
  • Hypertension, Pulmonary / metabolism*
  • Inflammation / genetics
  • Inflammation / immunology
  • Male
  • Middle Aged
  • Muscle, Smooth, Vascular / cytology
  • Muscle, Smooth, Vascular / metabolism*
  • Myocytes, Smooth Muscle / cytology
  • Myocytes, Smooth Muscle / metabolism
  • NADPH Oxidase 1 / metabolism
  • Oxidoreductases / metabolism
  • Pulmonary Artery / metabolism*
  • Superoxide Dismutase / metabolism
  • Tissue Array Analysis
  • Transcriptome
  • Vascular Remodeling / genetics

Substances

  • Oxidoreductases
  • Superoxide Dismutase
  • NADPH Oxidase 1
  • NOX1 protein, human
  • EZH2 protein, human
  • Enhancer of Zeste Homolog 2 Protein