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TGF-β1 Activates Nasal Fibroblasts through the Induction of Endoplasmic Reticulum Stress
(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 pres...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7355919/ https://www.ncbi.nlm.nih.gov/pubmed/32580467 http://dx.doi.org/10.3390/biom10060942 |
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author | Shin, Jae-Min Kang, Ju-Hyung Park, Joo-Hoo Yang, Hyun-Woo Lee, Heung-Man Park, Ii-Ho |
author_facet | Shin, Jae-Min Kang, Ju-Hyung Park, Joo-Hoo Yang, Hyun-Woo Lee, Heung-Man Park, Ii-Ho |
author_sort | Shin, Jae-Min |
collection | PubMed |
description | (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. |
format | Online Article Text |
id | pubmed-7355919 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-73559192020-07-22 TGF-β1 Activates Nasal Fibroblasts through the Induction of Endoplasmic Reticulum Stress Shin, Jae-Min Kang, Ju-Hyung Park, Joo-Hoo Yang, Hyun-Woo Lee, Heung-Man Park, Ii-Ho Biomolecules Article (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. MDPI 2020-06-22 /pmc/articles/PMC7355919/ /pubmed/32580467 http://dx.doi.org/10.3390/biom10060942 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Shin, Jae-Min Kang, Ju-Hyung Park, Joo-Hoo Yang, Hyun-Woo Lee, Heung-Man Park, Ii-Ho TGF-β1 Activates Nasal Fibroblasts through the Induction of Endoplasmic Reticulum Stress |
title | TGF-β1 Activates Nasal Fibroblasts through the Induction of Endoplasmic Reticulum Stress |
title_full | TGF-β1 Activates Nasal Fibroblasts through the Induction of Endoplasmic Reticulum Stress |
title_fullStr | TGF-β1 Activates Nasal Fibroblasts through the Induction of Endoplasmic Reticulum Stress |
title_full_unstemmed | TGF-β1 Activates Nasal Fibroblasts through the Induction of Endoplasmic Reticulum Stress |
title_short | TGF-β1 Activates Nasal Fibroblasts through the Induction of Endoplasmic Reticulum Stress |
title_sort | tgf-β1 activates nasal fibroblasts through the induction of endoplasmic reticulum stress |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7355919/ https://www.ncbi.nlm.nih.gov/pubmed/32580467 http://dx.doi.org/10.3390/biom10060942 |
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