Sulforaphane attenuates pulmonary fibrosis by inhibiting the epithelial-mesenchymal transition

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Background

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal disease with no effective treatment. The epithelial-mesenchymal transition (EMT) is a critical stage during the development of fibrosis. To assess the effect of sulforaphane (SFN) on the EMT and fibrosis using an in vitro transforming growth factor (TGF)-β1-induced model and an in vivo bleomycin (BLM)-induced model.

Methods

In vitro studies, cell viability, and cytotoxicity were measured using a Cell Counting Kit-8. The functional TGF-β1-induced EMT and fibrosis were assessed using western blotting and a quantitative real-time polymerase chain reaction. The lungs were analyzed histopathologically in vivo using hematoxylin and eosin and Masson’s trichrome staining. The BLM-induced fibrosis was characterized by western blotting and immunohistochemical analyses for fibronectin, TGF-β1, E-cadherin (E-cad), and α-smooth muscle actin (SMA) in lung tissues.

Results

SFN reversed mesenchymal-like changes induced by TGF-β1 and restored cells to their epithelial-like morphology. The results confirmed that the expression of the epithelial marker, E-cadherin, increased after SFN treatment, while expression of the mesenchymal markers, N-cadherin, vimentin, and α-SMA decreased in A549 cells after SFN treatment. In addition, SFN inhibited TGF-β1-induced mRNA expression of the EMT-related transcription factors, Slug, Snail, and Twist. The SFN treatment attenuated TGF-β1-induced expression of fibrosis-related proteins, such as fibronection, collagen I, collagen IV, and α-SMA in MRC-5 cells. Furthermore, SFN reduced the TGF-β1-induced phosphorylation of SMAD2/3 protein in A549 cells and MRC-5 cells. BLM induced fibrosis in mouse lungs that was also attenuated by SFN treatment, and SFN treatment decreased BLM-induced fibronectin expression, TGF-β1 expression, and the levels of collagen I in the lungs of mice.

Conclusions

SFN showed a significant anti-fibrotic effect in TGF-β-treated cell lines and BLM-induced fibrosis in mice. These findings showed that SFN has anti-fibrotic activity that may be considered in the treatment of IPF.

Electronic supplementary material

The online version of this article (10.1186/s40360-018-0204-7) contains supplementary material, which is available to authorized users.

Related collections

Most cited references 23

Record: found
Abstract: found
Article: not found

Epithelial-mesenchymal transitions in development and disease.

Jean Paul Thiery, Hervé Acloque, Ruby Y J Huang … (2009)

The epithelial to mesenchymal transition (EMT) plays crucial roles in the formation of the body plan and in the differentiation of multiple tissues and organs. EMT also contributes to tissue repair, but it can adversely cause organ fibrosis and promote carcinoma progression through a variety of mechanisms. EMT endows cells with migratory and invasive properties, induces stem cell properties, prevents apoptosis and senescence, and contributes to immunosuppression. Thus, the mesenchymal state is associated with the capacity of cells to migrate to distant organs and maintain stemness, allowing their subsequent differentiation into multiple cell types during development and the initiation of metastasis.

0 comments Cited 3687 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Idiopathic pulmonary fibrosis.

Luca Richeldi, Harold Collard, Mark G. Jones (2017)

Idiopathic pulmonary fibrosis is a prototype of chronic, progressive, and fibrotic lung disease. Healthy tissue is replaced by altered extracellular matrix and alveolar architecture is destroyed, which leads to decreased lung compliance, disrupted gas exchange, and ultimately respiratory failure and death. In less than a decade, understanding of the pathogenesis and management of this disease has been transformed, and two disease-modifying therapies have been approved, worldwide. In this Seminar, we summarise the presentation, pathophysiology, diagnosis, and treatment options available for patients with idiopathic pulmonary fibrosis. This disease has improved understanding of the mechanisms of lung fibrosis, and offers hope that similar approaches will transform the management of patients with other progressive fibrotic lung diseases.

0 comments Cited 662 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Idiopathic pulmonary fibrosis: prevailing and evolving hypotheses about its pathogenesis and implications for therapy.

M. Selman, T E King, A. Pardo (2001)

Idiopathic pulmonary fibrosis is a progressive and usually fatal lung disease characterized by fibroblast proliferation and extracellular matrix remodeling, which result in irreversible distortion of the lung's architecture. Although the pathogenetic mechanisms remain to be determined, the prevailing hypothesis holds that fibrosis is preceded and provoked by a chronic inflammatory process that injures the lung and modulates lung fibrogenesis, leading to the end-stage fibrotic scar. However, there is little evidence that inflammation is prominent in early disease, and it is unclear whether inflammation is relevant to the development of the fibrotic process. Evidence suggests that inflammation does not play a pivotal role. Inflammation is not a prominent histopathologic finding, and epithelial injury in the absence of ongoing inflammation is sufficient to stimulate the development of fibrosis. In addition, the inflammatory response to a lung fibrogenic insult is not necessarily related to the fibrotic response. Clinical measurements of inflammation fail to correlate with stage or outcome, and potent anti-inflammatory therapy does not improve outcome. This review presents a growing body of evidence suggesting that idiopathic pulmonary fibrosis involves abnormal wound healing in response to multiple, microscopic sites of ongoing alveolar epithelial injury and activation associated with the formation of patchy fibroblast-myofibroblast foci, which evolve to fibrosis. Progress in understanding the fibrogenic mechanisms in the lung is likely to yield more effective therapies.

0 comments Cited 385 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

Sun Young Kyung: light@gilhospital.com

Dae Young Kim: davekim@gachon.ac.kr

Jin Young Yoon: yjy0831@gilhospital.com

Eun Suk Son: eunsuk0607@hanmail.net

Yu Jin Kim: gene2001@gilhospital.com

Jeong Woong Park: jwpark@gilhospital.com

Sung Hwan Jeong: jsw@gilhospital.com

Journal

Journal ID (nlm-ta): BMC Pharmacol Toxicol

Journal ID (iso-abbrev): BMC Pharmacol Toxicol

Title: BMC Pharmacology & Toxicology

Publisher: BioMed Central (London )

ISSN (Electronic): 2050-6511

Publication date (Electronic): 2 April 2018

Publication date PMC-release: 2 April 2018

Publication date Collection: 2018

Volume: 19

Electronic Location Identifier: 13

Affiliations

[1 ]ISNI 0000 0004 0647 2885, GRID grid.411653.4, Department of Internal Medicine, , Gachon University Gil Medical Center, ; 21 Namdong-daero 774, Namdong-gu, Incheon, 21565 Republic of Korea

[2 ]ISNI 0000 0004 0647 2973, GRID grid.256155.0, Department of Biological Science, College of Bio-nano Technology, , Gachon University, ; Seongnam-daero 1342, Seongnam, South Korea

Article

Publisher ID: 204

DOI: 10.1186/s40360-018-0204-7

PMC ID: 5879815

PubMed ID: 29609658

SO-VID: bc64c2b9-3e14-4ac3-a134-6e5fa0373ae0

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

History

Date received : 30 November 2017

Date accepted : 21 March 2018

Funding

Funded by: FundRef http://dx.doi.org/10.13039/501100006107, Gachon University Gil Medical Center;

Award ID: 2013-34

Award Recipient : Sung Hwan Jeong

Custom metadata

ScienceOpen disciplines: Toxicology

Keywords: idiopathic pulmonary fibrosis,bleomycin,sulforaphane,epithelial-mesenchymal transition

Data availability:

ScienceOpen disciplines: Toxicology

Keywords: idiopathic pulmonary fibrosis, bleomycin, sulforaphane, epithelial-mesenchymal transition

Sulforaphane attenuates pulmonary fibrosis by inhibiting the epithelial-mesenchymal transition

Read this article at

Abstract

Background

Methods

Results

Conclusions

Electronic supplementary material

Related collections

Inflamed lung in vitro co-culture models

Most cited references 23

Epithelial-mesenchymal transitions in development and disease.

Idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis: prevailing and evolving hypotheses about its pathogenesis and implications for therapy.

Author and article information

Contributors

Journal

Affiliations

Article

History

Funding

Categories

Custom metadata

Comments

Comment on this article

Similar content 258

Cited by 32

Most referenced authors 692