Thymic stromal lymphopoietin induced early stage of epithelial-mesenchymal transition in human bronchial epithelial cells through upregulation of transforming growth factor beta 1

Cai, Liang‐Ming; Zhou, Yuqi; Yang, Lei; Qu, Jing-Xin; Dai, Zhen-Yuan; Li, Hongtao; Pan, Li; Ye, Hui-qing; Chen, Zhuang‐Gui

doi:10.1080/01902148.2019.1646841

Cited by 14 publications

(11 citation statements)

References 43 publications

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“…TSLP promotes allergic responses and airway remodeling 63 by acting on DCs, 55 thereby promoting the differentiation of naive CD4 + T cells into Th2 cells 64 , 65 and by inducing the survival of ILC2s 13 , 66 , 67 and the induction of epithelial‐mesenchymal transition (EMT) in airway epithelial cells. 68 Human lung fibroblasts are also a significant source of TSLP. 59 , 69 Through an autocrine mechanism, TSLP can activate human lung fibroblasts 70 to release type I collagen 71 and promote the proliferation of ASM cells.…”

Section: Airway Remodelingmentioning

confidence: 99%

Biologics and airway remodeling in severe asthma

Varricchi

Ferri

Pepys

et al. 2022

Allergy

121

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Asthma is a chronic inflammatory airway disease resulting in airflow obstruction, which in part can become irreversible to conventional therapies, defining the concept of airway remodeling. The introduction of biologics in severe asthma has led in some patients to the complete normalization of previously considered irreversible airflow obstruction. This highlights the need to distinguish a "fixed" airflow obstruction due to structural changes unresponsive to current therapies, from a "reversible" one as demonstrated by lung function normalization during biological therapies not previously obtained even with high-dose systemic glucocorticoids. The mechanisms by which exposure to environmental factors initiates the inflammatory responses that trigger airway remodeling are still incompletely understood. Alarmins represent epithelial-derived cytokines that initiate immunologic events leading to inflammatory airway remodeling. Biological therapies can improve airflow obstruction by addressing these airway inflammatory changes. In addition, biologics might prevent and possibly even revert "fixed" remodeling due to structural changes. Hence, it appears clinically important to separate the therapeutic effects (early and late) of biologics as a new paradigm to evaluate the effects of these drugs and future treatments on airway remodeling in severe asthma.

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Section: Airway Remodelingmentioning

confidence: 99%

Biologics and airway remodeling in severe asthma

Varricchi

Ferri

Pepys

et al. 2022

Allergy

121

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“…The data presented herein were consistent with that of previous report showing that blockage of TGF-β1 signaling inhibited TSLP-mediated EMT in human bronchial epithelial cells. 28 Therefore, TSLP induced the EMT in HNECs through TGF-β1 signaling.…”

Section: Discussionmentioning

confidence: 96%

“…The published report also demonstrated that TSLP induced TGF-β1 expression in human bronchial epithelial cells. 28 Hence, TSLP induced HNECs to produce TGF-β1.…”

Section: Discussionmentioning

confidence: 99%

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TSLP Induces Epithelial–Mesenchymal Transition in Nasal Epithelial Cells From Allergic Rhinitis Patients Through TGF-β1/Smad2/3 Signaling

Wang

Qian

et al. 2023

Am J Rhinol�Allergy

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Background Airway remodeling is demonstrated in Asian patients with allergic rhinitis (AR). The epithelial–mesenchymal transition (EMT) is one of the key mechanisms underlying airway remodeling. Thymic stromal lymphopoietin (TSLP) is an important contributor to airway remodeling. Although increased TSLP is found in AR, little is known about whether TSLP is involved in airway remodeling through induction of the EMT. Objective We investigated the effect of TSLP on the EMT in human nasal epithelial cells (HNECs) from AR patients. Methods Human nasal epithelial cells from AR patients were stimulated with TSLP in the absence or presence of the preincubation with a selective inhibitor of transforming growth factor beta 1 (TGF-β1) receptor (SB431542). The expression of TGF-β1 in the cells was evaluated by using real-time polymerase chain reaction, Western blotting, and immunocytochemistry. Western blotting and immunocytochemistry were used to assay EMT markers including vimentin, fibroblast-specific protein 1 (FSP1) and E-cadherin, small mothers against decapentaplegic homolog2/3 (Smad2/3), and phosphorylated Smad2/3 in the cells. The levels of extracellular matrix components such as collagens I and III in supernatants were measured by enzyme-linked immunoassay. Morphological changes of the cells were observed under inverted phase-contrast microscope. Results A concentration-dependent increase of TGF-β1 mRNA and protein was observed following stimulation with TSLP. Furthermore, TSLP decreased the expression of E-cadherin protein, but upregulated the production of FSP1 and vimentin proteins along with increased levels of collagens I and III, and the morphology of the cells was transformed into fibroblast-like shape. Additionally, a significant increase was found in phosphorylation of Smad2/3 protein. However, these effects were reversed by SB431542 preincubation. Conclusion TSLP–induced HNECs to undergo the EMT process via TGF-β1-mediated Smad2/3 activation. TSLP is an activator of the EMT in HNECs and might be a potential target for inhibiting EMT and reducing airway remodeling in AR.

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“…TSLP plays a role in airway remodeling 86 by promoting the differentiation of Th2 cells and innate lymphoid cells (ILCs) 13 and the induction of epithelial-mesenchymal transition (EMT) in airway epithelial cells 87 . Human lung fibroblasts are also a significant source of TSLP 83,88 .…”

Section: Airway Remodelingmentioning

confidence: 99%

Biologics and Airway Remodeling in Severe Asthma

Varricchi

Ferri

Pepys

et al. 2022

Preprint

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Asthma is a chronic inflammatory airway disease resulting in airflow obstruction, which in part can become irreversible to conventional therapies, defining the concept of airway remodeling. The introduction of biologics in severe asthma has led in some patients to the complete normalization of previously considered irreversible airflow obstruction. This highlights the need to distinguish a “fixed” bronchial obstruction due to structural changes unresponsive to current therapies, from a “reversible” one as demonstrated by lung function normalization during biological therapies not previously obtained even with high dose systemic glucocorticoids. The mechanisms by which exposure to environmental factors initiates the inflammatory responses that trigger airway remodeling are still incompletely understood. Alarmins represent tissue-derived cytokines that initiate immunologic events leading to inflammatory airway remodeling. Biological therapies can improve airflow obstruction by addressing these airway inflammatory changes. In addition, biologics might prevent and possibly even revert “fixed” remodeling due to structural changes. Hence, it appears clinically important to separate the therapeutic effects (early and late) of biologics as a new paradigm to evaluate the effects of these drugs and future treatments on airway remodeling in severe asthma.

show abstract

Thymic stromal lymphopoietin induced early stage of epithelial-mesenchymal transition in human bronchial epithelial cells through upregulation of transforming growth factor beta 1

Cited by 14 publications

References 43 publications

Biologics and airway remodeling in severe asthma

Biologics and airway remodeling in severe asthma

TSLP Induces Epithelial–Mesenchymal Transition in Nasal Epithelial Cells From Allergic Rhinitis Patients Through TGF-β1/Smad2/3 Signaling

Biologics and Airway Remodeling in Severe Asthma

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