Premium
Deficiency of urokinase plasminogen activator suppresses epithelial sodium channels in tracheal epithelial cells
Author(s) -
JI HONGLONG,
Chen Zaixing,
Liang Xinrong,
Zhao Runzhen,
Zhao Meimi
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1148.4
Subject(s) - epithelial sodium channel , plasmin , phosphorylation , chemistry , microbiology and biotechnology , plasminogen activator , downregulation and upregulation , proteases , activator (genetics) , endocrinology , biology , sodium , biochemistry , receptor , organic chemistry , gene , enzyme
Epithelial sodium channels (ENaC) govern transepithelial salt and fluid transport in tracheal, bronchi, and lungs. Fibrinolytic proteases play a crucial role in airway and lung injury and repair. We hypothesized that urokinase‐like plasminogen activator (uPA) regulates respiratory ENaC activity in primary mouse tracheal epithelial cells. The short‐circuit currents in confluent monolayer cells were compared between wild type and uPA null mice. Knockout of uPA led to depressed ENaC activity in both intact and permeabilized cells significantly. A significant decrease in Na + /K + ‐ATPase activity was observed as well. Application of uPA and plasmin partially restored ENaC activity and increased cleavage of alpha ENaC proteins in confluent monolayers. ERK1/2 but not Akt phosphorylation was augmented in uPA−/− cells and lungs. Taken together, uPA may regulate ENaC activity via multifaceted mechanisms, including proteolytic cleavage of α ENaC proteins, reduction in vectorial Na + driving force, and upregulation of ERK1/2 phosphorylation. Supported by NIH HL87017 and HL95435