Activation of the WNT/β-Catenin Pathway Attenuates Experimental Emphysema

Kneidinger, Nikolaus; Yildirim, Ali Önder; Callegari, Jens; Takenaka, Shinji; Stein, Maria Magdalena; Dumitrascu, Rio; Bohla, Alexander; Bracke, Ken R.; Morty, Rory E.; Brusselle, Guy; Schermuly, Ralph Theo; Eickelberg, Oliver; Königshoff, Mélanie

doi:10.1164/rccm.200910-1560oc

Cited by 169 publications

(193 citation statements)

References 128 publications

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“…Interestingly, it has been found that the mRNA levels of β-catenin were downregulated in the primary airway epithelium of smokers and smokers with COPD 13 and the number of β-catenin-positive staining alveolar epithelial cells were decreased in COPD patients compared with controls. 12 These studies suggested a crucial role of the WNT/β-catenin signaling in airway differentiation and alveolar tissue repair in COPD respectively. However, whether WNT/β-catenin signaling has an effect on CS-induced airway inflammation in COPD remains unclear.…”

Section: Discussionmentioning

confidence: 99%

“…10,11 Recently, WNT/β-catenin signaling has been implicated in tissue injury and the regeneration of COPD. [12][13][14] The activity of WNT/β-catenin signaling was decreased in the alveolar epithelial type II (ATII) cells of COPD patients and an emphysema mice model. 12 Wang et al 13 found that the expression profile of WNT/β-catenin signaling was decreased in the small airway epithelium of COPD patients and smokers, suggesting its important role in airway epithelium differentiation.…”

mentioning

confidence: 99%

“…[12][13][14] The activity of WNT/β-catenin signaling was decreased in the alveolar epithelial type II (ATII) cells of COPD patients and an emphysema mice model. 12 Wang et al 13 found that the expression profile of WNT/β-catenin signaling was decreased in the small airway epithelium of COPD patients and smokers, suggesting its important role in airway epithelium differentiation. In addition, TGF-β1-induced WNT/β-catenin signaling activation was enhanced in the lung fibroblasts of COPD subjects, indicating a role for WNT/β-catenin signaling in the fibroblast phenotype and extracellular matrix (ECM) production.…”

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confidence: 99%

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WNT/β-catenin signaling regulates cigarette smoke-induced airway inflammation via the PPARδ/p38 pathway

Guo

Wang

et al. 2016

Laboratory Investigation

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The mechanisms of WNT/β-catenin signaling involved in airway inflammation of chronic obstructive pulmonary disease (COPD) remain unknown, although recent observations have suggested an important contribution of the pathway in pulmonary parenchymal tissue repair and airway epithelium differentiation. We investigated the role of WNT/β-catenin signaling in cigarette smoke (CS)-related airway inflammation using patient lung tissues, human bronchial epithelial cells (16HBECs), and mouse models. Reduced activity of WNT/β-catenin signaling was observed in the airway epithelium of smokers with or without COPD. The mRNA expression of WNT transcription factor TCF4 negatively correlated with the pack year. The mRNA levels of WNT receptor FZD4 negatively correlated with the mRNA levels of IL-1β. CS exposure decreased the activity of WNT/β-catenin signaling in both 16HBECs and mice. In vitro studies demonstrated the upregulation of inflammatory cytokines TNF-α and IL-1β secretion induced by CS extract (CSE) could be attenuated by β-catenin activator SB216763 and be exacerbated by β-catenin small-interfering RNA (siRNA), respectively. Furthermore, the decrease in the expression of peroxisome proliferator-activated receptor (PPARδ) induced by CSE stimulation could be rescued by SB216763. SB216763 also attenuated the upregulation of phosphorylated p38 mitogen-activated protein kinase (MAPK) stimulated by CSE. Both PPARδ agonist and p38 MAPK inhibitor could suppress the TNF-α and IL-1β release induced by CSE treatment. In addition, PPARδ activation could abolish β-catenin siRNA-mediated aggravation of phosphorylated p38 MAPK in response to CSE. Finally, SB216763 treatment significantly ameliorated peribronchial inflammatory cell infiltration, leukocyte influx, and the release of TNF-α and IL-1β in the bronchoalveolar lavage fluid of CS-exposed mice. Taken together, our findings indicate that the reduced activity of WNT/β-catenin signaling induced by CS may promote inflammatory cytokine production in airway epithelium and have an essential role in airway inflammation in COPD by PPARδ/p38 MAPK pathway.

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Section: Discussionmentioning

confidence: 99%

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WNT/β-catenin signaling regulates cigarette smoke-induced airway inflammation via the PPARδ/p38 pathway

Guo

Wang

et al. 2016

Laboratory Investigation

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“…58 Therefore, LiCl has been widely used as a surrogate compound to assess the involvement of the Wnt/β-catenin pathway. [59][60][61][62][63][64] Interestingly, the current knowledge of the Wnt pathway can now explain clinical observation made even before the Wnt pathways have been described. Early case reports already demonstrated that treatment of patients suffering from chronic schizophrenia and asthma with LiCl not only reduced the manic episodes but also caused a reduction of asthma attacks and the use of asthma-specific medication, 65 and other clinical observations showed that stopping a long-lasting LiCl therapy in a patient-induced increased airway hyper-responsiveness and asthma symptoms.…”

Section: Immunological Role Of Wnt Pathways In Asthmamentioning

confidence: 99%

Take the Wnt out of the inflammatory sails: modulatory effects of Wnt in airway diseases

Reuter

Beckert

Taube

2016

Laboratory Investigation

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Bronchial asthma and chronic obstructive pulmonary disease (COPD) are chronic diseases that are associated with inflammation and structural changes in the airways and lungs. Recent findings have implicated Wnt pathways in critically regulating inflammatory responses, especially in asthma. Furthermore, canonical and noncanonical Wnt pathways are involved in structural changes such as airway remodeling, goblet cell metaplasia, and airway smooth muscle (ASM) proliferation. In COPD, Wnt pathways are not only associated with structural changes in the airways but also involved in the development of emphysema. The present review summarizes the role and function of the canonical and noncanonical Wnt pathway with regard to airway inflammation and structural changes in asthma and COPD. Further identification of the role and function of different Wnt molecules and pathways could help to develop novel therapeutic options for these diseases.

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“…Su sobreexpresión condiciona hiperplasia de células epiteliales alveolares con fibrosis pulmonar secundaria (en zonas de estrés mecánico) (21)(22)(23). En el enfisema se ha descrito inhibición de la vía Wnt mediada por productos de degradación del tabaco, que produce disminución en el número de células epiteliales alveolares con destrucción secundaria del parénquima pulmonar (23,24).…”

Section: Fisiopatologíaunclassified

Combinación de fibrosis pulmonar y enfisema: una entidad poco reconocida

Carrillo¹,

Morales-Cárdenas

Arias³

et al. 2016

rev. colomb. neumol.

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Objetivo : revisar definición, fisiopatología, manifestaciones clínicas, alteraciones enestudios de imágenes, pruebas de función pulmonar y pronóstico de los pacientes con combinaciónde fibrosis pulmonar y enfisema.Método : se realizó una revisión de la literatura en PubMed, para lo cual se usaron lostérminos MeSH: “fibrosis pulmonar”, “enfisema pulmonar” y la palabra “combinación”, limitandola búsqueda a la literatura publicada en los últimos cinco años. Para ilustrar la revisión seescogieron casos representativos de combinación de fibrosis pulmonar y enfisema estudiados ennuestra institución.Resultados : la búsqueda arrojó 163 referencias con los criterios seleccionados, se revisaron46 artículos en inglés, francés y español que se consideraron relevantes para el cumplimientodel objetivo de la revisión.Conclusiones: el término de combinación de fibrosis pulmonar y enfisema se refiere a la evidencia de enfisema y fibrosis en patología o en estudios de tomografía computarizada de alta resolución (tomografía computarizada de alta resolución). Inicialmente se describió en pacientes con patrón de neumonía intersticial usual y enfisema; sin embargo, se describe la coexistencia de fibrosis pulmonar y enfisema en pacientes con patrones de fibrosis pulmonar diferentes al de la neumonía intersticial usual. Los pacientes con combinación de fibrosis pulmonar y enfisema comparten antecedentes, manifestaciones clínicas, alteraciones radiológicas y pruebas de función pulmonar características, que difieren del grupo de pacientes con fibrosis pulmonar sin enfisema y aquellos con enfisema sin fibrosis. La morbimortalidad de aquellos con combinación de fibrosis pulmonar y enfisema difiere de la de los pacientes con enfisema o fibrosis pulmonar idiopática. Las opciones terapéuticas son limitadas.

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Activation of the WNT/β-Catenin Pathway Attenuates Experimental Emphysema

Cited by 169 publications

References 128 publications

WNT/β-catenin signaling regulates cigarette smoke-induced airway inflammation via the PPARδ/p38 pathway

WNT/β-catenin signaling regulates cigarette smoke-induced airway inflammation via the PPARδ/p38 pathway

Take the Wnt out of the inflammatory sails: modulatory effects of Wnt in airway diseases

Combinación de fibrosis pulmonar y enfisema: una entidad poco reconocida

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