Fibrosis contributes to 45% of all deaths in the developed world. It is a pathological form of tissue regeneration that features excessive connective tissue build-up, resulting in organ dysfunction and failure. Actin-controlled Myocardin related transcription factor (MRTF) and the Hippo pathway/cytoskeleton-regulated Transcriptional coactivator with PDZ-binding motif (TAZ) are two transcriptional co-activators that play key roles in fibrotic reprogramming. Previous work in the Kapus lab has demonstrated that MRTF and TAZ exhibit crosstalk regulating fibrotic gene expression. However, previous studies concentrated on nuclear translocation of TAZ as the key mechanism of its regulation, with few studies examining the signaling pathways and corresponding transcription factors controlling TAZ at the transcriptional level. This is a central question since increased TAZ expression is a major feature of many fibrotic diseases. This thesis aims to address this knowledge gap. Findings presented show that both chemical/soluble (TGFβ1) and mechanical (stretch) fibrogenic stimuli promote MRTF-dependent induction of TAZ transcription and thereby increase TAZ protein levels. TGFβ1 induces TAZ expression by increasing TAZ transcription (not stability) via smad3-independent, p38/MK2-dependent phosphorylation and activation of MRFT, which acts through the cis-element CArG box in the TAZ promoter. Importantly, TGFβ does not induce the expression of the TAZ paralog, YAP, defining a unique pathway for the regulation of TAZ. In addition to this novel translocation-independent mechanism, MRTF is regulated by actin polymerization-provoked translocation. This raises the intriguing possibility that Rho GTPases, key regulators of the actin cytoskeleton and important mechanotransducers, also control TAZ expression. Indeed, active Rho GTPases (RhoA, Rac1, Cdc42) and mechanical stimulation (cyclic stretch) induce MRTF-dependent TAZ promoter activation and TAZ expression. Since TGFβ also activates heat shock factor-1 (HSF1), a transcription factor with both pro- and anti-fibrotic effects, and the TAZ promoter contains HSF1-binding cis-elements (HSE), we tested if HSF1 regulates TAZ transcription. Interestingly, HSF1 suppresses MRTF-induced TAZ promoter activation. Taken together, these results define new mechanisms in the regulation of TAZ transcription/expression. MRTF, activated through distinct mechanisms by soluble (TGFβ) and mechanical (stretch) fibrogenic stimuli is a central mediator of this process, while HSF1 might act as an antifibrotic factor by counteracting the effect of MRTF on TAZ expression.