Effect of MeCP2 on TGF-β1-induced Extracellular Matrix Production in Nasal Polyp-derived Fibroblasts

Jae Min Shin, Ji Young Um, Seoung Ae Lee, Il Ho Park, Soo Hyung Lee, Heung Man Lee

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Purpose: Methyl-CpG-binding protein 2 (MeCP2), known as a transcriptional regulator, has been suggested to play an important role in myofibroblast differentiation in the lung. The purpose of this study was to investigate the role of MeCP2 in transforming growth factor (TGF)-β1-induced myofibroblast differentiation and extracellular matrix (ECM) production in nasal polyp-derived fibroblasts (NPDFs). Methods: To identify the expression of MeCP2 in nasal polyp tissues, immunohistochemistry staining and Western blot were performed. TGF-β1-induced NPDFs were treated with 5-azacytidine, a DNA methylation inhibitor, and the expression levels of α-SMA and fibronectin were determined by semiquantitative reverse transcription polymerase chain reaction, immunofluorescent staining, and Western blotting. The total soluble collagen was analyzed by the Sircol collagen assay. MeCP2 silenced by MeCP2-specific small interference (si) RNA was verified by Western blot. Results: The expression levels of MeCP2 increased in nasal polyp tissues compared to normal inferior turbinate tissues. 5-Azacytidine significantly inhibited the expression of α-SMA and fibronectin mRNA in a dose-dependent manner. In addition, 5-azacytidine suppressed collagen production and the expression of MeCP2 in the same manner. The expression levels of a-SMA and collagen production were significantly blocked by MeCP2 silencing in TGF-β1-induced NPDFs. Conclusions: Our data suggest that MeCP2 plays an essential role in TGF-β1-induced myofibroblast differentiation and ECM production in NPDFs.

Original languageEnglish
Pages (from-to)228-235
Number of pages8
JournalAmerican Journal of Rhinology and Allergy
Volume32
Issue number4
DOIs
Publication statusPublished - 2018 Jul 1

Keywords

  • extracellular matrix
  • MeCP2
  • myofibroblast
  • nasal polyp
  • TGF-β1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Otorhinolaryngology

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