CCG-257081
and modulation of pirin decrease SMAD2 phosphorylation
and MRTF-A nuclear localization. (A) Left panel: Representative Western
blot of p-SMAD2, total SMAD2, and GAPDH of lysates from primary human
primary dermal fibroblasts after cotreatment with 10 μM CCG-257081
and 10 ng/mL TGF-β for 24 h. Right panel: Quantification of
left panel. The results are expressed as the overall mean as well
as mean values from three independent experiments. *, p < 0.05 using a ratio paired t test. (B) Human
primary dermal fibroblasts were infected with virus containing shRNA
against LacZ (shPirin −) or Pirin (shPirin +). Cells were then
treated with 10 ng/mL TGF-β for 24 h, and Western blotting was
performed for p-SMAD2, total SMAD2, and GAPDH. Right panel: quantification
of left panel. Bars represent overall mean with paired independent
means, n = 3. (C) Cells infected with shLacZ or shPirin
were plated in 8-well chamber slides and then were treated with 10
ng/mL TGF-β in 0.5% FBS+DMEM and stained for endogenous MRTF-A.
Scale bar represents 200 μm. (D) Quantification of (C) with
the percentage of total cells with exclusively nuclear MRTF-A, n = 3. The overall mean is shown (bars). Total number of
cells counted in each experimental condition was >200.