Pyocyanin-induced mucin production is associated with redox modification of FOXA2

Hao, Yonghua; Kuang, Zhizhou; Xu, Ying; Walling, Brent E.; Lau, Gee W.

doi:10.1186/1465-9921-14-82

Cited by 37 publications

(53 citation statements)

References 65 publications

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“…Normal human bronchial epithelial (NHBE) cells were purchased from Lonza (Walkersville, MD) and cultured as we have previously described (18,20). Cells were thawed and passaged in 5% CO 2 at 37°C with bronchial epithelial growth medium (BEGM) supplemented with growth factors supplied in the SingleQuot kit (Lonza).…”

Section: Methodsmentioning

confidence: 99%

“…Mouse lungs were processed as described previously (18,20). Briefly, a cannula was inserted into the trachea and the lungs were instilled with 10% neutral buffered formalin at a constant pressure (25 cm H 2 O).…”

Section: Methodsmentioning

confidence: 99%

“…Airway epithelial cells grown in ALI culture have emerged as a powerful tool for the study of airway biology. For example, we have shown that P. aeruginosa pyocyanin induces ALI cultures of NHBE cells to secrete MUC5AC and MUC5B, major mucins found in healthy and diseased human airways (18,20). We examined if M. pneumoniae M129 could induce the expression of MUC5AC and MUC5B in an ALI culture of NHBE cells.…”

Section: Pneumoniae Induces the Expression Of Mucins In Nci-h292 Cmentioning

confidence: 99%

“…Previously, we have shown that Pseudomonas aeruginosa induces goblet cell hyperplasia and metaplasia (GCHM) and mucus hypersecretion by secreting the redox-active toxin pyocyanin, which induces STAT6 and epidermal growth factor receptor (EGFR) signaling to inactivate FOXA2, a major transcriptional repressor of GCHM and mucin biosynthesis (18,19). Pyocyanin also redox inactivates FOXA2 through posttranslational modifications, resulting in the overexpression of mucins (20). Importantly, the expression of FOXA2 is depleted in the airways of bronchiectatic and asthmatic patients, as well as in the ovalbumin-induced mouse model of asthma (19,21).…”

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confidence: 99%

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Mycoplasma pneumoniae Modulates STAT3-STAT6/EGFR-FOXA2 Signaling To Induce Overexpression of Airway Mucins

et al. 2014

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cAberrant mucin secretion and accumulation in the airway lumen are clinical hallmarks associated with various lung diseases such as asthma, chronic obstructive pulmonary disease, and cystic fibrosis. Mycoplasma pneumoniae, long appreciated as one of the triggers of acute exacerbations of chronic pulmonary diseases, has recently been reported to promote excessive mucus secretion. However, the mechanism of mucin overproduction induced by M. pneumoniae remains unclear. This study aimed to determine the mechanism by which M. pneumoniae induces mucus hypersecretion by using M. pneumoniae infection of mouse lungs, human primary bronchial epithelial (NHBE) cells cultured at the air-liquid interface, and the conventionally cultured airway epithelial NCI-H292 cell line. We demonstrated that M. pneumoniae induced the expression of mucins MUC5AC and MUC5B by activating the STAT6-STAT3 and epidermal growth factor receptor (EGFR) signal pathways, which in turn downregulated FOXA2, a transcriptional repressor of mucin biosynthesis. The upstream stimuli of these pathways, including interleukin-4 (IL-4), IL-6, and IL-13, increased dramatically upon exposure to M. pneumoniae. Inhibition of the STAT6, STAT3, and EGFR signaling pathways significantly restored the expression of FOXA2 and attenuated the expression of airway mucins MUC5AC and MUC5B. Collectively, these studies demonstrated that M. pneumoniae induces airway mucus hypersecretion by modulating the STAT/EGFR-FOXA2 signaling pathways.A irway mucus forms a protective coating that entraps foreign particles and microbes, facilitating their clearance by mucociliary transport. Mucus is composed mainly of mucin glycoproteins, water, ions, and cellular debris. Mucins are the major macromolecular component of the mucus gel responsible for its viscoelastic, rheological, and clearance properties. MUC5AC and MUC5B are the major mucins of human airways (1-3). Although a deficient mucous barrier intuitively leaves the lungs vulnerable to injury, aberrant mucin secretion and accumulation contribute significantly to the pathogenesis of airway diseases such as asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis (CF) (1-4). Mucus plugging in asthmatic and COPD lungs is a major cause of airway narrowing and death (5, 6). Furthermore, hypersecretion of MUC5AC is detrimental during acute lung injury (7).The ability of microbial pathogens to induce mucus secretion suggests that it is one of the mechanisms of infection-induced exacerbation in airway diseases (8-11). M. pneumoniae is the most common cause of community-acquired pneumonia. Moreover, M. pneumoniae has long been recognized as a trigger of both chronic infection and acute exacerbation in multiple chronic airway diseases, including asthma (12, 13). Several virulence mechanisms of M. pneumoniae are known, including cytoadherence through a polar attachment organelle (14), generation of reactive oxygen species (ROS) (15), and secretion of the community-acquired respiratory distress syndrome (CARDS) toxin (16). Alth...

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Pneumoniae Induces the Expression Of Mucins In Nci-h292 Cmentioning

confidence: 99%

mentioning

confidence: 99%

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Mycoplasma pneumoniae Modulates STAT3-STAT6/EGFR-FOXA2 Signaling To Induce Overexpression of Airway Mucins

et al. 2014

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“…lipotoxin [241] metallo-β-Lactamase antimicrobial resistance factor [242] PcrV (type III secretion system) virulence factor [243] phenazine and derivates virulence factor [244][245][246] Pseudomonas aeruginosa pseudoverdine virulence factor [247] pyochelin (siderophore) virulence factor [248] pyocyanin (phenazide) virulence factor [223,[249][250][251][252][253][254][255][256][257][258][259][260][261][262] pyoluteorin [263] pyoverdine virulence factor [227,[264][265][266] rhamnolipids bacterial surfactants [227,267] Tse2 virulence factor [268] TypA virulence factor [269] Type II secretion system virulence factor [270] Type III secretion system virulence factor [271- …”

Section: Microorganism Secondary Metabolites Commentsmentioning

confidence: 99%

Database on the taxonomical characterisation and potential toxigenic capacities of microorganisms used for the industrial production of food enzymes and feed additives, which do not have a recommendation for Qualified Presumption of Safety

Benito

Ibáñez

Moncho

et al. 2017

EFSA Supporting Publications

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The present work constitutes the external scientific report of the EFSA open call OC/EFSA/FEED/2015/01. The aim of the call was to provide EFSA with a database from a review on the taxonomical description and potential toxigenic capacities of microorganisms used for the industrial production of feed additives and food enzymes. The review includes microorganisms used as source of feed additives and food enzymes for which EFSA has received or can potentially receive applications for safety assessment, and which have not been recommended for Qualified Presumption of Safety status. The database also comprises the molecular taxonomical identifiers and biosynthetic pathways involved in the production of toxic compounds and the responsible genes. The main result of the project is shown as a database developed according to the EFSA data structure. The methodological aspects and the queries used in the systematic search, as well as the procedure applied for the screening of scientific documents retrieved are described in this report. Details are available in supplementary appendices.In total, 22970 scientific documents were screened in the literature search, from which 411 were initially selected for providing pertinent data for the scope of the project. From the review of the selected articles, 474 bioactive secondary metabolites were recorded and 59 compounds were further studied in order to obtain data on their toxicology and the conditions in which they are produced by the microorganisms used in industrial fermentations. The database generated in this project comprises details that characterise, when available, the production conditions, genes involved and toxicity of these 59 compounds. This provides information that can be used to establish safety measures when using potentially toxigenic microorganisms in industrial fermentations Disclaimer: The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Acknowledgements:We thank the following EFSA satff: Jaime Aguilera, Margarita Aguilera-Gómez, Jane Richardson, Mario Monguidi and Davide Gibin for their valuable help and collaboration throughout the project. We also would like to thank the members of AINIA: Sonia Porta, Lidia Tomás, Joaquin Espí and Juan Antonio Nieto for providing expertise in biotechnology and molecular biology and contributing with their efforts to achieve the goals of this project, and Violeta Gómez from the University of Navarra for her colla...

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FOXA2 Suppression by TRIM36 Exerts Anti‐Tumor Role in Colorectal Cancer Via Inducing NRF2/GPX4‐Regulated Ferroptosis

Liu,

Yan,

Chang

et al. 2023

Advanced Science

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The forkhead box transcription factor A2 (FOXA2) is a transcription factor and plays a key role in embryonic development, metabolism homeostasis and tumor cell proliferation; however, its regulatory potential in CRC is not fully understood. Here, it is found that FOXA2 expression is markedly up‐regulated in tumor samples of CRC patients as compared with the normal tissues, which is closely associated with the worse survival in patients with CRC. Notably, a positive correlation between FOXA2 and nuclear factor erythroid 2‐related factor 2 (Nrf2)/glutathione peroxidase 4 (GPX4) gene expression is observed in CRC patients. Mechanistically, FOXA2 depletion weakens the activation of Nrf2 pathway and decreases GPX4 level in CRC cells, thereby leading to ferroptosis, which is further supported by bioinformatic analysis. More intriguingly, the E3 ubiquitin ligase tripartite motif containing 36 (TRIM36) is identified as a key suppressor of FOXA2, and it is observed that TRIM36 can directly interact with FOXA2 and induce its K48‐linked polyubiquitination, resulting in FOXA2 protein degradation in vitro. Taken together, all the studies demonstrate that FOXA2 mediated by TRIM36 promotes CRC progression by inhibiting the Nrf2/GPX4 ferroptosis signaling pathway, thus providing a new therapeutic target for CRC treatment.

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Pyocyanin-induced mucin production is associated with redox modification of FOXA2

Cited by 37 publications

References 65 publications

Mycoplasma pneumoniae Modulates STAT3-STAT6/EGFR-FOXA2 Signaling To Induce Overexpression of Airway Mucins

Mycoplasma pneumoniae Modulates STAT3-STAT6/EGFR-FOXA2 Signaling To Induce Overexpression of Airway Mucins

Database on the taxonomical characterisation and potential toxigenic capacities of microorganisms used for the industrial production of food enzymes and feed additives, which do not have a recommendation for Qualified Presumption of Safety

FOXA2 Suppression by TRIM36 Exerts Anti‐Tumor Role in Colorectal Cancer Via Inducing NRF2/GPX4‐Regulated Ferroptosis

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