Tgf-β1 activates nasal fibroblasts through the induction of endoplasmic reticulum stress

Jae Min Shin, Ju Hyung Kang, Joo Hoo Park, Hyun Woo Yang, Heung Man Lee, Ii Ho Park

Research output: Contribution to journalArticlepeer-review

Abstract

(1) Background: Tissue remodeling and extracellular matrix (ECM) accumulation contribute to the development of chronic inflammatory diseases of the upper airway. Endoplasmic reticulum (ER) stress is considered to be the key signal for triggering tissue remodeling in pathological conditions. The present study aimed to investigate the role of ER-stress in TGF-β1-stimulated nasal fibroblasts and inferior turbinate organ cultures; (2) Methods: Fibroblasts and organ cultures were pretreated with 4-phenylbutyric acid (PBA) and stimulated with TGF-β1 or thapsigargin (TG). Expression of ER-stress markers, myofibroblast marker, and ECM components was measured by Western blotting and real-time PCR. Reactive oxygen species (ROS) were quantified using 2,7-dichlorofluorescein diacetate. Cell migration was evaluated using Transwell assays. Contractile activity was measured by collagen contraction assay; (3) Results: 4-PBA inhibited TGF-β1 or TG-induced ER-stress marker expression, phenotypic changes, and ECM. Pre-treatment with ROS scavengers inhibited the expression of TGF-β1-induced ER-stress markers. Migration and collagen contraction of TGF-β1 or TG-stimulated fibroblasts were ameliorated by 4-PBA treatment. These findings were confirmed in ex vivo organ cultures; (4) Conclusions: 4-PBA downregulates TGF-β1-induced ER-stress marker expression, migration, and collagen contraction via ROS in fibroblasts and organ cultures. These results suggest that ER-stress may play an important role in progression of chronic upper airway inflammatory diseases by aiding pathological tissue remodeling.

Original languageEnglish
Article number942
Pages (from-to)1-13
Number of pages13
JournalBiomolecules
Volume10
Issue number6
DOIs
Publication statusPublished - 2020 Jun

Keywords

  • Airway remodeling
  • Extracellular matrix
  • Fibroblast
  • Nose
  • Transforming growth factor beta-1
  • Unfolded protein response

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

Fingerprint Dive into the research topics of 'Tgf-β1 activates nasal fibroblasts through the induction of endoplasmic reticulum stress'. Together they form a unique fingerprint.

Cite this