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

Autor: Nguyen Thu Ngan Trinh, Ryszard Grygorczyk, Anik Privé, Emmanuelle Brochiero, Jasmine Chebli, Émilie Maillé, Alban Girault
Rok vydání: 2015
Předmět:
Pulmonary and Respiratory Medicine
Male
Pathology
medicine.medical_specialty
Time Factors
Lung injury
Biology
Transfection
Rats
Sprague-Dawley
Alveolar cells
Extracellular matrix
03 medical and health sciences
Transient receptor potential channel
0302 clinical medicine
Cell Movement
Potassium Channel Blockers
medicine
Animals
Cells
Cultured
Cell Proliferation
TRPC Cation Channels
030304 developmental biology
Wound Healing
0303 health sciences
Dose-Response Relationship
Drug
Integrin beta1
Research
Calcium channel
Intermediate-Conductance Calcium-Activated Potassium Channels
Fibronectins
Cell biology
Pulmonary Alveoli
Fibronectin
medicine.anatomical_structure
Alveolar Epithelial Cells
030220 oncology & carcinogenesis
biology.protein
RNA Interference
Signal transduction
Wound healing
Signal Transduction
Zdroj: Respiratory Research
ISSN: 1465-993X
Popis: 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.
Databáze: OpenAIRE
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