The role of Glucocerebrosidase GBA2 in cystic fibrosis lung inflammation: from molecular mechanism to therapeutic strategies

2016 ◽  
Author(s):  
Aureli M et al
Keyword(s):  
Cystic Fibrosis ◽  
Molecular Mechanism ◽  
Lung Inflammation ◽  
Therapeutic Strategies ◽  
Cystic Fibrosis Lung

scholarly journals S-palmitoylation regulates biogenesis of core glycosylated wild-type and F508del CFTR in a post-ER compartment

2014 ◽  
Vol 459 (2) ◽  
pp. 417-425 ◽  
Author(s):  
Michelle L. McClure ◽  
Hui Wen ◽  
James Fortenberry ◽  
Jeong S. Hong ◽  
Eric J. Sorscher
Keyword(s):  
Cystic Fibrosis ◽  
Molecular Target ◽  
Therapeutic Strategies ◽  
Common Disease ◽  
Wild Type ◽  
New Evidence

This study provides new evidence that palmitoylation contributes to CFTR trafficking and participates during rescue of a common disease-associated mutation. Therapeutic strategies to overcome clinically important defects in cystic fibrosis should consider the role of palmitoylation as a molecular target.

scholarly journals In vitro and in vivo evidence for an inflammatory role of the calcium channel TRPV4 in lung epithelium: Potential involvement in cystic fibrosis

2016 ◽  
Vol 311 (3) ◽  
pp. L664-L675 ◽  
Author(s):  
Clémence O. Henry ◽  
Emilie Dalloneau ◽  
Maria-Teresa Pérez-Berezo ◽  
Cristina Plata ◽  
Yongzheng Wu ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Calcium Channel ◽  
Lung Inflammation ◽  
Transient Receptor Potential ◽  
Biologically Active ◽  
Transient Receptor Potential Vanilloid ◽  
Anti Inflammatory

Cystic fibrosis (CF) is an inherited disease associated with chronic severe lung inflammation, leading to premature death. To develop innovative anti-inflammatory treatments, we need to characterize new cellular and molecular components contributing to the mechanisms of lung inflammation. Here, we focused on the potential role of “transient receptor potential vanilloid-4” (TRPV4), a nonselective calcium channel. We used both in vitro and in vivo approaches to demonstrate that TRPV4 expressed in airway epithelial cells triggers the secretion of major proinflammatory mediators such as chemokines and biologically active lipids, as well as a neutrophil recruitment in lung tissues. We characterized the contribution of cytosolic phospholipase A2, MAPKs, and NF-κB in TRPV4-dependent signaling. We also showed that 5,6-, 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acids, i.e., four natural lipid-based TRPV4 agonists, are present in expectorations of CF patients. Also, TRPV4-induced calcium mobilization and inflammatory responses were enhanced in cystic fibrosis transmembrane conductance regulator-deficient cellular and animal models, suggesting that TRPV4 is a promising target for the development of new anti-inflammatory treatments for diseases such as CF.

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