Eosinophils Promote Epithelial to Mesenchymal Transition of Bronchial Epithelial Cells

Yasukawa, Atsushi; Hosoki, Koa; Toda, Masaaki; Miyake, Yohei; Matsushima, Yuki; Μatsumoto, Takahiro; Boveda-Ruiz, Daniel; Gil-Bernabe, Paloma; Nagao, Mizuho; Sugimoto, Mayumi; Hiraguchi, Yukiko; Tokuda, Reiko; Naito, Makoto; Takagi, Takehiro; D’Alessandro-Gabazza, Corina N.; Suga, Shigeru; Kobayashi, Tetsu; Fujisawa, Takao; Taguchi, Osamu; Gabazza, Esteban C.

doi:10.1371/journal.pone.0064281

Cited by 56 publications

(65 citation statements)

References 38 publications

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“…TGF-β1 might also contribute to enhance airway remodeling through EMT. Indeed, anti-TGF-β1 treatment inhibits EMT in airway epithelial cells (Yasukawa et al, 2013). …”

Section: Airway Epitheliummentioning

confidence: 99%

Pathology of asthma

Kudo¹,

Ishigatsubo²,

Aoki³

2013

Front. Microbiol.

294

213

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Asthma is a serious health and socioeconomic issue all over the world, affecting more than 300 million individuals. The disease is considered as an inflammatory disease in the airway, leading to airway hyperresponsiveness, obstruction, mucus hyper-production and airway wall remodeling. The presence of airway inflammation in asthmatic patients has been found in the nineteenth century. As the information in patients with asthma increase, paradigm change in immunology and molecular biology have resulted in an extensive evaluation of inflammatory cells and mediators involved in the pathophysiology of asthma. Moreover, it is recognized that airway remodeling into detail, characterized by thickening of the airway wall, can be profound consequences on the mechanics of airway narrowing and contribute to the chronic progression of the disease. Epithelial to mesenchymal transition plays an important role in airway remodeling. These epithelial and mesenchymal cells cause persistence of the inflammatory infiltration and induce histological changes in the airway wall, increasing thickness of the basement membrane, collagen deposition and smooth muscle hypertrophy and hyperplasia. Resulting of airway inflammation, airway remodeling leads to the airway wall thickening and induces increased airway smooth muscle mass, which generate asthmatic symptoms. Asthma is classically recognized as the typical Th2 disease, with increased IgE levels and eosinophilic inflammation in the airway. Emerging Th2 cytokines modulates the airway inflammation, which induces airway remodeling. Biological agents, which have specific molecular targets for these Th2 cytokines, are available and clinical trials for asthma are ongoing. However, the relatively simple paradigm has been doubted because of the realization that strategies designed to suppress Th2 function are not effective enough for all patients in the clinical trials. In the future, it is required to understand more details for phenotypes of asthma.

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“…TGF-β1 might also contribute to enhance airway remodeling through EMT. Indeed, anti-TGF-β1 treatment inhibits EMT in airway epithelial cells (Yasukawa et al, 2013). …”

Section: Airway Epitheliummentioning

confidence: 99%

Pathology of asthma

Kudo¹,

Ishigatsubo²,

Aoki³

2013

Front. Microbiol.

294

213

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“…Likely candidates include leukocytes, platelets, endothelial cells and cancer associated fibroblasts (CAFs) [54–57]. Immunohistochemical staining in breast cancer suggests that the microvessels in the vicinity of invading cancer cells may be a critical factor for adapting an EMT phenotype although the paracrine mechanisms contributing to this effect have not been fully elucidated [46].…”

Section: Cellular and Molecular Alteration During Emtmentioning

confidence: 99%

Epithelial Plasticity During Human Breast Morphogenesis and Cancer Progression

Ingþórsson

Briem

Bergþórsson

et al. 2016

J Mammary Gland Biol Neoplasia

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Understanding the complex events leading to formation of an epithelial-based organ such as the breast requires a detailed insight into the crosstalk between epithelial and stromal compartments. These interactions occur both through heterotypic cellular interactions and between cells and matrix components. While in vivo models may partially capture these complex interactions, there is a need for in- vitro models to study these events. In this review we discuss cell-cell interactions in breast development focusing on the stem cell niche and branching morphogenesis. Given the recent understanding that the basic developmental events underlying branching morphogenesis are closely related to pathways important to cancer progression, i.e. epithelial plasticity and epithelial to mesenchymal transition (EMT), we will also discuss aspects relevant to cancer progression. In cancer, the adoption of mesenchymal phenotype by the malignant cells allows stromal invasion and subsequent intravasation to blood- or lymphatic vessels, a route that is a prerequisite for metastasis. A number of publications have demonstrated that tumor initiating cells, sometimes referred to as cancer stem cells adapt an EMT phenotype that renders them more resistant to apoptosis and drug therapy. The mechanism behind this phenomenon is currently unknown but this may partially explain relapse in breast cancer patients. Increased understanding of branching morphogenesis in the breast gland and the regulation of EMT and its reverse process mesenchymal to epithelial transition (MET) may hold the keys for future development of methods/drugs that neutralize the invading properties of cancer cells.

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“…Moreover, in a murine asthma model, EMT was shown to occur in response to prolonged allergen exposure [86]. Mediated by TGF-b, eosinophils have been shown to induce EMT when co-cultured with human epithelial cells and also when placed in the trachea of a murine model [87]. Despite all this evidence, EMT has yet to be demonstrated in asthma in vivo.…”

Section: The Epithelium In Asthmamentioning

confidence: 99%

Asthma Therapy and Its Effect on Airway Remodelling

Berair

Brightling

2014

Drugs

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Asthma remains a major health problem with significant morbidity, mortality and economic costs. In asthma, airway remodelling, which refers to all the microscopic structural changes seen in the airway tissue, has been recognised for many decades and remains one of the defining characteristics of the disease; however, it is still poorly understood. The detrimental pathophysiological consequences of some features of remodelling, like increased airway smooth muscle mass and subepithelial fibrosis, are well documented. However, whether targeting these by therapy would be beneficial is unknown. Although the prevailing thinking is that remodelling is an abnormal response to persistent airway inflammation, recent evidence, especially from studies of remodelling in asthmatic children, suggests that the two processes occur in parallel. The effects of asthma therapy on airway remodelling have not been studied extensively due to the challenges of obtaining airway tissue in the context of clinical trials. Corticosteroids remain the cornerstone of asthma therapy, and their effects on remodelling have been better studied than other drugs. Bronchial thermoplasty is the only asthma therapy to primarily target remodelling, although how it results in the apparent clinical benefits seen is not exactly clear. In this article we discuss the mechanisms of airway remodelling in asthma and review the effects of conventional and novel asthma therapies on the process.

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Eosinophils Promote Epithelial to Mesenchymal Transition of Bronchial Epithelial Cells

Cited by 56 publications

References 38 publications

Pathology of asthma

Pathology of asthma

Epithelial Plasticity During Human Breast Morphogenesis and Cancer Progression

Asthma Therapy and Its Effect on Airway Remodelling

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