Combined control of the fibroblast contractile program by YAP and TAZ

YAP and TAZ are transcription cofactors implicated in the contractile and pro-fibrotic activation of fibroblasts. Fibroblast contractile function is important in alveologenesis, as well as in lung wound healing and fibrosis. As paralogs, YAP and TAZ may have independent or redundant roles in regulating transcriptional programs and contractile function. Using IMR-90 lung fibroblasts, microarray analysis and traction microscopy we tested whether independent YAP or TAZ knockdown alone was sufficient to limit transcriptional activation and contraction in vitro. IMR-90 cells were stimulated with TGFβ1 (2 ng/ml) for 72 hours in the presence of scrambled, YAP, TAZ or both YAP and TAZ siRNA (n=3 replicates per condition). Transcript levels were evaluated using the Affymetrix GeneChip PrimeView Human Gene Expression Array. Transcripts changed by more than 2-fold with a p-value<0.05 were analyzed using Ingenuity Pathway Analysis