Update on Calcium Signaling in Cystic Fibrosis Lung Disease
Cystic fibrosis (CF) is an autosomal recessive disorder characterized by mutations in the cystic fibrosis transmembrane conductance regulator gene, which causes multifunctional defects that preferentially affect the airways. Abnormal viscosity of mucus secretions, persistent pathogen infections, hyp...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-03-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2021.581645/full |
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| author | Alessandro Rimessi Alessandro Rimessi Veronica A. M. Vitto Simone Patergnani Paolo Pinton Paolo Pinton |
| author_facet | Alessandro Rimessi Alessandro Rimessi Veronica A. M. Vitto Simone Patergnani Paolo Pinton Paolo Pinton |
| author_sort | Alessandro Rimessi |
| collection | DOAJ |
| description | Cystic fibrosis (CF) is an autosomal recessive disorder characterized by mutations in the cystic fibrosis transmembrane conductance regulator gene, which causes multifunctional defects that preferentially affect the airways. Abnormal viscosity of mucus secretions, persistent pathogen infections, hyperinflammation, and lung tissue damage compose the classical pathological manifestation referred to as CF lung disease. Among the multifunctional defects associated with defective CFTR, increasing evidence supports the relevant role of perturbed calcium (Ca2+) signaling in the pathophysiology of CF lung disease. The Ca2+ ion is a critical player in cell functioning and survival. Its intracellular homeostasis is maintained by a fine balance between channels, transporters, and exchangers, mediating the influx and efflux of the ion across the plasma membrane and the intracellular organelles. An abnormal Ca2+ profile has been observed in CF cells, including airway epithelial and immune cells, with heavy repercussions on cell function, viability, and susceptibility to pathogens, contributing to proinflammatory overstimulation, organelle dysfunction, oxidative stress, and excessive cytokines release in CF lung. This review discusses the role of Ca2+ signaling in CF and how its dysregulation in airway epithelial and immune cells contributes to hyperinflammation in the CF lung. Finally, we provide an outlook on the therapeutic options that target the Ca2+ signaling to treat the CF lung disease. |
| first_indexed | 2024-12-17T08:41:32Z |
| format | Article |
| id | doaj.art-d5972956c1b44360a0e039a6f0df8fe9 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-17T08:41:32Z |
| publishDate | 2021-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-d5972956c1b44360a0e039a6f0df8fe92022-12-21T21:56:19ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-03-011210.3389/fphar.2021.581645581645Update on Calcium Signaling in Cystic Fibrosis Lung DiseaseAlessandro Rimessi0Alessandro Rimessi1Veronica A. M. Vitto2Simone Patergnani3Paolo Pinton4Paolo Pinton5Department of Medical Sciences and Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara, Ferrara, ItalyCenter of Research for Innovative Therapies in Cystic Fibrosis, University of Ferrara, Ferrara, ItalyDepartment of Medical Sciences and Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara, Ferrara, ItalyDepartment of Medical Sciences and Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara, Ferrara, ItalyDepartment of Medical Sciences and Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara, Ferrara, ItalyCenter of Research for Innovative Therapies in Cystic Fibrosis, University of Ferrara, Ferrara, ItalyCystic fibrosis (CF) is an autosomal recessive disorder characterized by mutations in the cystic fibrosis transmembrane conductance regulator gene, which causes multifunctional defects that preferentially affect the airways. Abnormal viscosity of mucus secretions, persistent pathogen infections, hyperinflammation, and lung tissue damage compose the classical pathological manifestation referred to as CF lung disease. Among the multifunctional defects associated with defective CFTR, increasing evidence supports the relevant role of perturbed calcium (Ca2+) signaling in the pathophysiology of CF lung disease. The Ca2+ ion is a critical player in cell functioning and survival. Its intracellular homeostasis is maintained by a fine balance between channels, transporters, and exchangers, mediating the influx and efflux of the ion across the plasma membrane and the intracellular organelles. An abnormal Ca2+ profile has been observed in CF cells, including airway epithelial and immune cells, with heavy repercussions on cell function, viability, and susceptibility to pathogens, contributing to proinflammatory overstimulation, organelle dysfunction, oxidative stress, and excessive cytokines release in CF lung. This review discusses the role of Ca2+ signaling in CF and how its dysregulation in airway epithelial and immune cells contributes to hyperinflammation in the CF lung. Finally, we provide an outlook on the therapeutic options that target the Ca2+ signaling to treat the CF lung disease.https://www.frontiersin.org/articles/10.3389/fphar.2021.581645/fullinflammatory diseasecalcium signalinglung diseaseinflammationcystic fibrosiscalcium |
| spellingShingle | Alessandro Rimessi Alessandro Rimessi Veronica A. M. Vitto Simone Patergnani Paolo Pinton Paolo Pinton Update on Calcium Signaling in Cystic Fibrosis Lung Disease Frontiers in Pharmacology inflammatory disease calcium signaling lung disease inflammation cystic fibrosis calcium |
| title | Update on Calcium Signaling in Cystic Fibrosis Lung Disease |
| title_full | Update on Calcium Signaling in Cystic Fibrosis Lung Disease |
| title_fullStr | Update on Calcium Signaling in Cystic Fibrosis Lung Disease |
| title_full_unstemmed | Update on Calcium Signaling in Cystic Fibrosis Lung Disease |
| title_short | Update on Calcium Signaling in Cystic Fibrosis Lung Disease |
| title_sort | update on calcium signaling in cystic fibrosis lung disease |
| topic | inflammatory disease calcium signaling lung disease inflammation cystic fibrosis calcium |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2021.581645/full |
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