The role of uPAR in epithelial-mesenchymal transition in small airway epithelium of patients with chronic obstructive pulmonary disease

Wang, Qin; Wang, Yunshan; Zhang, Yi; Zhang, Yuke; Xiao, Wei

doi:10.1186/1465-9921-14-67

Cited by 86 publications

(94 citation statements)

References 39 publications

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“…Our data demonstrated the downregulation of E-cadherin and upregulation of vimentin in small airway epithelium of the COPD lungs, indicating the active EMT in small airways of COPD patients. These results are consistent with previous findings that EMT contributed to remodelling of small airways in COPD (3,30,31). Up to date, there are limited data regarding the potential role of FXR in EMT.…”

Section: Discussionsupporting

confidence: 83%

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Overexpression of farnesoid X receptor in small airways contributes to epithelial to mesenchymal transition and COX-2 expression in chronic obstructive pulmonary disease

Bi¹,

You²,

Xue³

et al. 2016

J. Thorac. Dis.

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Background: Epithelial-mesenchymal transition (EMT) and cyclooxygenase-2 (COX-2) contribute to airway remodelling and inflammation in chronic obstructive pulmonary disease (COPD). Recent data suggest that the farnesoid X receptor (FXR), a nuclear receptor traditionally considered as bile acid-activated receptor, is also expressed in non-classical bile acids target tissues with novel functions beyond regulating bile acid homeostasis. This study aimed to investigate the potential role of FXR in the development of COPD, as well as factors that affect FXR expression. Conclusions: Overexpression of FXR in small airway may contribute to airway remodelling and inflammation in COPD by regulating EMT and COX-2 expression.

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Section: Discussionsupporting

confidence: 83%

“…However, airway remodelling in COPD, such as peribronchiolar fibrosis, is mainly located in small airways. Furthermore, the large and small airways have different anatomical and pathophysiological characteristics (30). Therefore, the role of active EMT in small airways remains to be elucidated.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of farnesoid X receptor in small airways contributes to epithelial to mesenchymal transition and COX-2 expression in chronic obstructive pulmonary disease

Bi¹,

You²,

Xue³

et al. 2016

J. Thorac. Dis.

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“…27 We have recently shown that increased uPAR expression in the small airway epithelium of COPD patients participates in an active EMT process modulated by PI3K/ Akt and GSK3b. 17 uPAR is a glycosyl phosphatidylinositolanchored protein with a high affinity to uPA. The uPAR expression and its ability to bind uPA are required for signaling.…”

Section: Discussionmentioning

confidence: 99%

“…These results are consistent with our previous reports in intracellular that uPAR is increasing in CSE-induced cells. 17 …”

Section: Increased Upa Expression In Cse-induced Hsaepic Cellsmentioning

confidence: 99%

“…16 We have recently described a pathway through which cigarette smoke extract (CSE) induces EMT in human small airway epithelial cells by increasing uPAR expression and activating uPAR-dependent cell signaling pathways. 17 We have investigated the effect and mechanism of uPA action on EMTs in human small airway epithelium of COPD patients, and explored the interaction between uPA and uPAR on EMTs.…”

mentioning

confidence: 99%

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Involvement of urokinase in cigarette smoke extract-induced epithelial–mesenchymal transition in human small airway epithelial cells

Wang

Zhang

et al. 2015

Laboratory Investigation

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Urokinase-type plasminogen activator (uPA) augments inflammation and tissue remodeling during lung injury and repair. The uPA expression in small airway epithelium of chronic obstructive pulmonary disease (COPD) increases. Epithelialmesenchymal transition (EMT) is important in the small airway fibrosis of COPD. This study shows the uPA regulation in cigarette smoke extract (CSE)-induced EMT in human small airway epithelial cell lines (HSAEpiCs). uPA is overexpressed in the small airway epithelium of COPD patients and CSE-treated cell lines. Furthermore, uPA expression correlated with vimentin expression in the small airway epithelium of COPD patients. uPA inhibition blocks CSE-induced EMT by reversing E-cadherin and a-catenin expression and retarding the induction of N-cadherin and vimentin, resulting in reduction in migration. uPA overexpression in HSAEpiC cells also promotes EMT and migration. EMT is partly reversed in uPA-overexpressing HSAEpiC cells through the silencing expression of uPA receptor. In conclusion, this study provides new insights into the contribution of uPA upregulation to EMT associated with small airway remodeling in COPD.

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Elevated PLAUR is observed in the airway epithelium of asthma patients and blocking improves barrier integrity

Portelli,

Bhaker,

Pang

et al. 2023

Clinical & Translational All

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BackgroundExpression of the urokinase plasminogen activator receptor (uPAR) is elevated in the airway epithelium in asthma; however, the contribution of uPAR to asthma pathogenesis and scope for therapeutic targeting remains unknown.ObjectivesTo determine (i) the expression profile of uPAR in cultured human bronchial epithelial cells (HBEC) from asthma patients, (ii) the relationship between uPAR and the epithelial barrier, including blocking uPAR functions and (iii) the function of different uPAR isoforms.MethodsuPAR levels in HBECs isolated from asthma patients and cells at air liquid interface (ALI) during differentiation were quantified. Transepithelial electrical resistance or electrical cell impedance sensing was used to relate uPAR levels to barrier properties, including effects of uPAR blocking antibodies. The functional effects of gain of function was determined using transcriptomics, in cells over‐expressing membrane (muPAR), soluble cleaved (scuPAR) or soluble spliced (ssuPAR) isoforms.ResultsElevated expression of uPAR was a feature of cultured HBECs from asthma patients, suggesting intrinsic alterations in asthma patient cells. Soluble uPAR levels inversely correlated with barrier properties of the HBEC layer in 2D and ALI. Blocking uPAR‐integrin interactions enhanced barrier formation. The gain of function cells showed limited transcriptomic changes.ConclusionThis study provides a significant advance in our understanding of the relationship between asthma, uPAR and the epithelial barrier, where elevated circulating uPAR results in a reduced cell barrier, a phenotype prevalent in asthma.

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The role of uPAR in epithelial-mesenchymal transition in small airway epithelium of patients with chronic obstructive pulmonary disease

Cited by 86 publications

References 39 publications

Overexpression of farnesoid X receptor in small airways contributes to epithelial to mesenchymal transition and COX-2 expression in chronic obstructive pulmonary disease

Overexpression of farnesoid X receptor in small airways contributes to epithelial to mesenchymal transition and COX-2 expression in chronic obstructive pulmonary disease

Involvement of urokinase in cigarette smoke extract-induced epithelial–mesenchymal transition in human small airway epithelial cells

Elevated PLAUR is observed in the airway epithelium of asthma patients and blocking improves barrier integrity

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