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Respiratory Research
Published in: Respiratory Research 1/2015

Open Access 01-12-2015 | Research

Complementary roles of KCa3.1 channels and β1-integrin during alveolar epithelial repair

Authors: Alban Girault, Jasmine Chebli, Anik Privé, Nguyen Thu Ngan Trinh, Emilie Maillé, Ryszard Grygorczyk, Emmanuelle Brochiero

Published in: Respiratory Research | Issue 1/2015

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Abstract

Background

Extensive alveolar epithelial injury and remodelling is a common feature of acute lung injury and acute respiratory distress syndrome (ARDS) and it has been established that epithelial regeneration, and secondary lung oedema resorption, is crucial for ARDS resolution. Much evidence indicates that K+ channels are regulating epithelial repair processes; however, involvement of the KCa3.1 channels in alveolar repair has never been investigated before.

Results

Wound-healing assays demonstrated that the repair rates were increased in primary rat alveolar cell monolayers grown on a fibronectin matrix compared to non-coated supports, whereas an anti-β1-integrin antibody reduced it. KCa3.1 inhibition/silencing impaired the fibronectin-stimulated wound-healing rates, as well as cell migration and proliferation, but had no effect in the absence of coating. We then evaluated a putative relationship between KCa3.1 channel and the migratory machinery protein β1-integrin, which is activated by fibronectin. Co-immunoprecipitation and immunofluorescence experiments indicated a link between the two proteins and revealed their cellular co-distribution. In addition, we demonstrated that KCa3.1 channel and β1-integrin membrane expressions were increased on a fibronectin matrix. We also showed increased intracellular calcium concentrations as well as enhanced expression of TRPC4, a voltage-independent calcium channel belonging to the large TRP channel family, on a fibronectin matrix. Finally, wound-healing assays showed additive effects of KCa3.1 and TRPC4 inhibitors on alveolar epithelial repair.

Conclusion

Taken together, our data demonstrate for the first time complementary roles of KCa3.1 and TRPC4 channels with extracellular matrix and β1-integrin in the regulation of alveolar repair processes.
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Metadata
Title
Complementary roles of KCa3.1 channels and β1-integrin during alveolar epithelial repair
Authors
Alban Girault
Jasmine Chebli
Anik Privé
Nguyen Thu Ngan Trinh
Emilie Maillé
Ryszard Grygorczyk
Emmanuelle Brochiero
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Respiratory Research / Issue 1/2015
Electronic ISSN: 1465-993X
DOI
https://doi.org/10.1186/s12931-015-0263-x

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