jun-N-terminal kinase regulates thrombin-induced PAI-1 gene expression in proximal tubular epithelial cells

摘要

jun-N-terminal kinase regulates thrombin-induced PAI-1 gene expression in proximal tubular epithelial cells.BackgroundInterstitial activation of the coagulation cascade is a common finding in acute and chronic tubulointerstitial damage. We previously demonstrated that thrombin may induce proximal tubular epithelial cells (PTEC) proliferation and regulate, through plasminogen activator inhibitor (PAI)-1 and urokinase-type plasminogen activator (u-PA), their profibrotic activity. The signaling pathways leading to these effects are still unknown. The PAI-1 promoter contains several activator protein-1 (AP-1) consensus sequences. AP-1 activation is induced by different agonists through jun-N-terminal kinase (JNK). Thus, we investigated the role of the JNK-AP-1 axis on thrombin-induced PAI-1 and u-PA expression in immortalized PTEC and its modulation by PKC and src, two key signaling enzymes.