Figure 3

GGTI-286 mimics the effects of simvastatin on TGFβ1-induced fibronectin protein expression. Western analysis was performed using whole cell lysates obtained from primary human airway fibroblast cultures that were maintained under TGFβ1 (2.5 ng/ml)-stimulated or serum-deprived conditions in the absence or presence of simvastatin (10 μM), GGTI-286 (10 μM) or FTI-277 (10 μM) for 48 h. (A) Representative western blots showing that the suppressive effects of simvastatin on TGFβ1-induced fibronectin protein expression could be mimicked by GGTI-286, but not by FTI-277. (B) Bar chart summarizing the effects of simvastatin, GGTI-286 and FTI-277 under basal and TGFβ1-stimulated conditions on fibronectin protein abundance. (C) Reverse transcriptase PCR was performed using total RNA extracted from human fibroblast cell cultures. The photograph shows that transcripts for 7 prenyl transferase subunits are abundant in these cells, including multiple variants of the FNTA subunit that is common to GGT1 and FT. Data in panel B represent means ± s.e. mean of 3 independent experiments, using 3 different cell lines. Legend: 0 h and t = 0: initial basal (unstimulated) cultures; 48 h and t = 48 h: treatment time-matched, basal (unstimulated) cultures; C: cells treated with TGFβ1 alone for 48 hours; Simv: simvastatin. **P < 0.01 compared to C(ontrol).