β-Elemene inhibits the proliferation of primary human airway granulation fibroblasts by down-regulating canonical Wnt/β-catenin pathway

Benign airway stenosis is a clinical challenge because of recurrent granulation tissues. Our previous study proved that a Chinese drug, β-elemene, could effectively inhibit the growth of fibroblasts cultured from hyperplastic human airway granulation tissues, which could slow down the progression of...

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Main Authors: Xue, Cheng, Hong, Ling-Ling, Lin, Jun-Sheng, Yao, Xiang-Yang, Wu, Ding-Hui, Lin, Xiao-Ping, Zhang, Jia-Min, Zhang, Xiao-Bin, Zeng, Yi-Ming
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Publicado em: Portland Press Ltd. 2018
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Research Articles
Acesso em linha:https://ncbi.nlm.nih.gov/pmc/articles/PMC5835718/
https://ncbi.nlm.nih.gov/pubmed/29358311
https://ncbi.nlm.nih.govhttp://dx.doi.org/10.1042/BSR20171386
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spelling pubmed-58357182018-03-20 β-Elemene inhibits the proliferation of primary human airway granulation fibroblasts by down-regulating canonical Wnt/β-catenin pathway Xue, Cheng Hong, Ling-Ling Lin, Jun-Sheng Yao, Xiang-Yang Wu, Ding-Hui Lin, Xiao-Ping Zhang, Jia-Min Zhang, Xiao-Bin Zeng, Yi-Ming Biosci Rep Research Articles Benign airway stenosis is a clinical challenge because of recurrent granulation tissues. Our previous study proved that a Chinese drug, β-elemene, could effectively inhibit the growth of fibroblasts cultured from hyperplastic human airway granulation tissues, which could slow down the progression of this disease. The purpose of the present study is to find out the mechanism for this effect. We cultured fibroblasts from normal human airway tissues and human airway granulation tissues. These cells were cultured with 160 μg/ml normal saline (NS), different doses of β-elemene, or 10 ng/ml canonical Wnt/β-catenin pathway inhibitor (Dickkopf-1, DKK-1). The proliferation rate of cells and the expression of six molecules involved in canonical Wnt/β-catenin pathway, Wnt3a, glycogen synthase kinase-3β (GSK-3β), β-catenin, α-smooth muscle actin (α-SMA), transforming growth factor-β (TGF-β), and Collagen I (Col-I), were measured. At last, we used canonical Wnt/β-catenin pathway activator (LiCl) to further ascertain the mechanism of β-elemene. Canonical Wnt/β-catenin pathway is activated in human airway granulation fibroblasts. β-Elemene didn’t affect normal human airway fibroblasts; however, it had a dose–responsive inhibitive effect on the proliferation and expression of Wnt3a, non-active GSK-3β, β-catenin, α-SMA, TGF-β, and Col-I of human airway granulation fibroblasts. More importantly, it had the same effect on the expression and nuclear translocation of active β-catenin. All these effects were similar to 10 ng/ml DKK-1 and could be attenuated by 10 mM LiCl. Thus, β-elemene inhibits the proliferation of primary human airway granulation fibroblasts by down-regulating canonical Wnt/β-catenin pathway. This pathway is possibly a promising target to treat benign tracheobronchial stenosis. Portland Press Ltd. 2018-04-13 /pmc/articles/PMC5835718/ /pubmed/29358311 http://dx.doi.org/10.1042/BSR20171386 Text en © 2018 The Author(s). http://creativecommons.org/licenses/by/4.0/This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY) (http://creativecommons.org/licenses/by/4.0/) .
institution US NLM
collection PubMed Central
language Inglês
format Artigo
topic Research Articles
spellingShingle Research Articles
Xue, Cheng
Hong, Ling-Ling
Lin, Jun-Sheng
Yao, Xiang-Yang
Wu, Ding-Hui
Lin, Xiao-Ping
Zhang, Jia-Min
Zhang, Xiao-Bin
Zeng, Yi-Ming
β-Elemene inhibits the proliferation of primary human airway granulation fibroblasts by down-regulating canonical Wnt/β-catenin pathway
description Benign airway stenosis is a clinical challenge because of recurrent granulation tissues. Our previous study proved that a Chinese drug, β-elemene, could effectively inhibit the growth of fibroblasts cultured from hyperplastic human airway granulation tissues, which could slow down the progression of this disease. The purpose of the present study is to find out the mechanism for this effect. We cultured fibroblasts from normal human airway tissues and human airway granulation tissues. These cells were cultured with 160 μg/ml normal saline (NS), different doses of β-elemene, or 10 ng/ml canonical Wnt/β-catenin pathway inhibitor (Dickkopf-1, DKK-1). The proliferation rate of cells and the expression of six molecules involved in canonical Wnt/β-catenin pathway, Wnt3a, glycogen synthase kinase-3β (GSK-3β), β-catenin, α-smooth muscle actin (α-SMA), transforming growth factor-β (TGF-β), and Collagen I (Col-I), were measured. At last, we used canonical Wnt/β-catenin pathway activator (LiCl) to further ascertain the mechanism of β-elemene. Canonical Wnt/β-catenin pathway is activated in human airway granulation fibroblasts. β-Elemene didn’t affect normal human airway fibroblasts; however, it had a dose–responsive inhibitive effect on the proliferation and expression of Wnt3a, non-active GSK-3β, β-catenin, α-SMA, TGF-β, and Col-I of human airway granulation fibroblasts. More importantly, it had the same effect on the expression and nuclear translocation of active β-catenin. All these effects were similar to 10 ng/ml DKK-1 and could be attenuated by 10 mM LiCl. Thus, β-elemene inhibits the proliferation of primary human airway granulation fibroblasts by down-regulating canonical Wnt/β-catenin pathway. This pathway is possibly a promising target to treat benign tracheobronchial stenosis.
author Xue, Cheng
Hong, Ling-Ling
Lin, Jun-Sheng
Yao, Xiang-Yang
Wu, Ding-Hui
Lin, Xiao-Ping
Zhang, Jia-Min
Zhang, Xiao-Bin
Zeng, Yi-Ming
author_facet Xue, Cheng
Hong, Ling-Ling
Lin, Jun-Sheng
Yao, Xiang-Yang
Wu, Ding-Hui
Lin, Xiao-Ping
Zhang, Jia-Min
Zhang, Xiao-Bin
Zeng, Yi-Ming
author_sort Xue, Cheng
title β-Elemene inhibits the proliferation of primary human airway granulation fibroblasts by down-regulating canonical Wnt/β-catenin pathway
title_short β-Elemene inhibits the proliferation of primary human airway granulation fibroblasts by down-regulating canonical Wnt/β-catenin pathway
title_full β-Elemene inhibits the proliferation of primary human airway granulation fibroblasts by down-regulating canonical Wnt/β-catenin pathway
title_fullStr β-Elemene inhibits the proliferation of primary human airway granulation fibroblasts by down-regulating canonical Wnt/β-catenin pathway
title_full_unstemmed β-Elemene inhibits the proliferation of primary human airway granulation fibroblasts by down-regulating canonical Wnt/β-catenin pathway
title_sort β-elemene inhibits the proliferation of primary human airway granulation fibroblasts by down-regulating canonical wnt/β-catenin pathway
publisher Portland Press Ltd.
container_title Biosci Rep
publishDate 2018
url https://ncbi.nlm.nih.gov/pmc/articles/PMC5835718/
https://ncbi.nlm.nih.gov/pubmed/29358311
https://ncbi.nlm.nih.govhttp://dx.doi.org/10.1042/BSR20171386
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