(Pro)renin Receptor-Dependent Induction of Profibrotic Factors Is Mediated by COX-2/EP4/NOX-4/Smad Pathway in Collecting Duct Cells.

ABSTRACT: The binding of prorenin to the (pro)renin receptor (PRR) triggers the activation of MAPK/ERK1/2 pathway, induction of cyclooxygenase-2 (COX-2), NOX-4-dependent production of reactive oxygen species (ROS), and the induction of transforming growth factor β (TGF-β) and profibrotic factors connecting tissue growth factor (CTGF) and plasminogen activator inhibitor (PAI-I) in collecting duct (CD) cells. However, the role of COX-2 and the intracellular pathways involved are not clear. We hypothesized that the PRR activation increases profibrotic factors through COX-2-mediated PGE2 activation of E prostanoid receptor 4 (EP4), upregulation of NOX-4/ROS production, and activation of Smad pathway in mouse CD cells. Recombinant prorenin increased ROS production and protein levels of CTGF, PAI-I, and T

SUBMITTER: Reyes-Martinez C 

PROVIDER: S-EPMC6664006 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature