Dual Role of RACK1 in Airway Epithelial Cells: A Concomitant Regulator of TGF-β1 Induced Apoptosis and Epithelial Mesenchymal Transition

2019 ◽  
Author(s):  
Yue Pu ◽  
Yuan-qi Liu ◽  
Yan Zhou ◽  
Yi-fan Qi ◽  
Shi-ping Liao ◽  
...  



2011 ◽  
Vol 177 (3) ◽  
pp. 241-246 ◽  
Author(s):  
Li Bai ◽  
Zubin Yu ◽  
Changzheng Wang ◽  
Guisheng Qian ◽  
Guansong Wang


2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Linjie Chen ◽  
Xiaobai He ◽  
Yan Xie ◽  
Yapei Huang ◽  
Dennis W. Wolff ◽  
...  


2009 ◽  
Vol 20 (22) ◽  
pp. 4751-4765 ◽  
Author(s):  
Ewa Kolosionek ◽  
Rajkumar Savai ◽  
Hossein Ardeschir Ghofrani ◽  
Norbert Weissmann ◽  
Andreas Guenther ◽  
...  

Epithelial–mesenchymal transition (EMT) has emerged as a critical event in the pathogenesis of organ fibrosis and cancer and is typically induced by the multifunctional cytokine transforming growth factor (TGF)-β1. The present study was undertaken to evaluate the potential role of phosphodiesterases (PDEs) in TGF-β1-induced EMT in the human alveolar epithelial type II cell line A549. Stimulation of A549 with TGF-β1 induced EMT by morphological alterations and by expression changes of the epithelial phenotype markers E-cadherin, cytokeratin-18, zona occludens-1, and the mesenchymal phenotype markers, collagen I, fibronectin, and α-smooth muscle actin. Interestingly, TGF-β1 stimulation caused twofold increase in total cAMP-PDE activity, contributed mostly by PDE4. Furthermore, mRNA and protein expression demonstrated up-regulation of PDE4A and PDE4D isoforms in TGF-β1-stimulated cells. Most importantly, treatment of TGF-β1 stimulated epithelial cells with the PDE4-selective inhibitor rolipram or PDE4 small interfering RNA potently inhibited EMT changes in a Smad-independent manner by decreasing reactive oxygen species, p38, and extracellular signal-regulated kinase phosphorylation. In contrast, the ectopic overexpression of PDE4A and/or PDE4D resulted in a significant loss of epithelial marker E-cadherin but did not result in changes of mesenchymal markers. In addition, Rho kinase signaling activated by TGF-β1 during EMT demonstrated to be a positive regulator of PDE4. Collectively, the findings presented herein suggest that TGF-β1 mediated up-regulation of PDE4 promotes EMT in alveolar epithelial cells. Thus, targeting PDE4 isoforms may be a novel approach to attenuate EMT-associated lung diseases such as pulmonary fibrosis and lung cancer.



PLoS ONE ◽  
2016 ◽  
Vol 11 (1) ◽  
pp. e0146365 ◽  
Author(s):  
Laura Leone ◽  
Francesca Mazzetta ◽  
Daniela Martinelli ◽  
Sabatino Valente ◽  
Maurizio Alimandi ◽  
...  


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