Effects of histone deacetylase inhibitor on extracellular matrix production in human nasal polyp organ cultures

Jung Sun Cho, You Mi Moon, Il Ho Park, Ji Young Um, Ju Hyung Kang, Tae-Hoon Kim, Sang Hag Lee, Hee Joon Kang, Heung Man Lee

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Background: Nasal polyposis is associated with a chronic inflammatory condition of the sinonasal mucosa and involves myofibroblast differentiation and extracellular matrix (ECM) accumulation. Epigenetic modulation by histone deacetylase (HDAC) inhibitors including trichostatin A (TSA) has been reported to have inhibitory effects on myofibroblast differentiation in lung and renal fibroblasts. The purpose of this study was to investigate the inhibitory effect of TSA on myofibroblast differentiation and ECM production in nasal polyp organ cultures. Methods: Nasal polyp tissues from 18 patients were acquired during endoscopic sinus surgery. After organ culture, nasal polyps were stimulated with TGF-beta1 and then treated with TSA. Alpha-smooth muscle actin (=-SMA), fibronectin, and collagen type I expression levels were examined by reverse transcription-polymerase chain reaction (PCR), real-time PCR, Western blot, and immunofluorescent staining. HDAC2, HDAC4, and acetylated H4 expression levels were assayed by Western blot. Cytotoxicity was analyzed by the terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling assay. Results: The expression levels of =-SMA, fibronectin, and collagen type 1 were increased in nasal polyp after transforming growth factor (TGF) beta1 treatment. TSA-inhibited TGF-beta1 induced these gene and protein expression levels. Furthermore, TSA suppressed protein expression levels of HDAC2 and HDAC4. However, TSA induced hyperacetylation of histones H4. Treatment with TGF-beta1 with or without TSA did not have cytotoxic effect. Conclusion: These findings provide novel insights into the epigenetic regulation in myofibroblast differentiation and ECM production of nasal polyp. TSA could be a candidate of a therapeutic agent for reversing the TGF-beta1-induced ECM synthesis that leads to nasal polyp development.

Original languageEnglish
Pages (from-to)18-23
Number of pages6
JournalAmerican Journal of Rhinology and Allergy
Volume27
Issue number1
DOIs
Publication statusPublished - 2013 Jan 1

Fingerprint

trichostatin A
Nasal Polyps
Histone Deacetylase Inhibitors
Organ Culture Techniques
Extracellular Matrix
Transforming Growth Factor beta1
Myofibroblasts
Collagen Type I
Fibronectins
Epigenomics
Western Blotting
DNA Nucleotidylexotransferase
Biotin
Nose
Histones
Reverse Transcription
Smooth Muscle
Actins
Real-Time Polymerase Chain Reaction
Mucous Membrane

ASJC Scopus subject areas

  • Otorhinolaryngology
  • Immunology and Allergy

Cite this

Effects of histone deacetylase inhibitor on extracellular matrix production in human nasal polyp organ cultures. / Cho, Jung Sun; Moon, You Mi; Park, Il Ho; Um, Ji Young; Kang, Ju Hyung; Kim, Tae-Hoon; Lee, Sang Hag; Kang, Hee Joon; Lee, Heung Man.

In: American Journal of Rhinology and Allergy, Vol. 27, No. 1, 01.01.2013, p. 18-23.

Research output: Contribution to journalArticle

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AU - Kang, Hee Joon

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