Figure 3.

Shear stress response in PTECs is modulated by ALK4/5/7 and MEK1/2 inhibitors. Relative expression of selected genes upon 16 hr fluid shear stress exposure, as measured by quantitative PCR. (a) ALK4/5/7 inhibitor (10 μM LY‐364947) significantly reduces shear stress increased expression of Junb, Wisp1, Map3k20, Map4k4, Ets1, Plk2, Prune2, and Fbln5, while shear stress induced down‐regulation of Jak2 and Stat1 was not altered. (b) MEK1/2 inhibition (10 μM Trametinib) significantly reduces shear stress increased expression of Plk2 and Fbln5, while fluid‐flow increased expression of Junb, Map3k20, Ets1, and Prune2 is further elevated. Wisp1 and Map4k4 expression was not altered upon MEK inhibition. Jak2 and Stat1 expression was still down‐regulated by shear stress upon MEK inhibition, although basal levels were slightly higher. (a, b) Parallel plate flow‐chamber induced fluid shear stress at 2.0 dyn/cm² in PTECs; t = 16 hr; qPCR, Hprt served as housekeeping gene to correct for cDNA input; data normalized to unstimulated controls (fold change); n = 3–5 per condition. *Indicates p < 0.05 by two‐way ANOVA, followed by post‐hoc Fisher's LSD multiple comparison. ALK‐inh = ALK4/5/7 inhibitor (LY‐364947). MEK‐inh = MEK1/2 inhibitor (Trametinib, GSK1120212)