Matrix metalloproteinases 2 and 9 reduce epithelial sodium channel (ENaC) activity at pleural mesothelium

摘要

The aim of the study was to investigate if Matrix metalloproteinase 2 (MMP2) and Matrix metalloproteinase 9 (MMP9) influence epithelial sodium channel (ENaC) current. Pleural membranes from sheep were mounted at Ussing chambers and were voltage-clamped. MMP2 and MMP9 were applied apically to the pleural membranes and amiloride was added to all experiments. All values are expressed as mean ± standard error of mean (SEM). In control experiments, the short circuit current (Isc) amiloride-sensitive was 7.6 ± 1.6 μΑ/cm2. At concentrations 0.0001 and 0.1 ng/ml, non-statistical significant differences occurred whereas at concentration 10 ng/ml, MMP2 and MMP9 increased the Isc amiloride-sensitive to 15 ± 2.8 and 18 ± 3.1 μA/cm2,?respectively. This increase was statistically significant (p = 0.0016 and 0.0021, respectively). At concentration 20 ng/ml, MMP2 and MMP9 decreased significantly the Isc amiloride-sensitive to 2.8 ± 0.7 and 3 ± 0.7 μΑ/cm2, respectively. These results demonstrated that MMPs act biphasically; at lower concentrations, they increase ENaC activity and thus they enhance sodium and water absorption from pleural cavity whereas at higher concentrations they hinder ENaC activity and thus aggregate pleural fluid formation.