Figure 5.

E-Prostanoid receptor 4 blockade prevents hrPR-induced ROS accumulation, NOX-4 upregulation, and induction of profibrotic factors CTGF, TGF-β, and PAI-I. Another set of M-1 cells was tested for ROS production and protein expression of NOX-4, CTGF, TGF-β, and PAI-I. Pre-incubations with 10⁷ M of L-161982 partially prevented ROS induction (A) and upregulation of profibrotic factors (B). NOX-4 induction was prevented by EP4 L-161982 (C). Because NOX-4 is responsible for ROS production and TGF-β synthesis, we tested the activation of Smad pathway by examining phosphorylation of Smad2 and 3. Preincubations with EP4 inhibitor prevented Smad2 and 3 phosphorylation levels in response to hrPR incubations (D).