Plasmin improves blood-gas barrier function in oedematous lungs by cleaving epithelial sodium channels.

ABSTRACT:

Background and purpose

Lung oedema in association with suppressed fibrinolysis is a hallmark of lung injury. Here, we have tested whether plasmin cleaves epithelial sodium channels (ENaC) to resolve lung oedema fluid.

Experimental approach

Human lungs and airway acid-instilled mice were used for analysing fluid resolution. In silico prediction, mutagenesis, Xenopus oocytes, immunoblotting, voltage clamp, mass spectrometry, and protein docking were combined for identifying plasmin cleavage sites.

Key results

Plasmin improved lung fluid resolution in both human lungs ex vivo and injured mice. Plasmin activated αβγENaC channels in oocytes in a time-dependent manner. Deletion of four consensus proteolysis tracts (αΔ432-444, γΔ131-138, γΔ178-193, and γΔ410-422) eliminated

SUBMITTER: Zhao R 

PROVIDER: S-EPMC7280014 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature