Although it has been disputed, the transition of epithelial phenotype to a mesenchymal phenotype is considered as one of the sources of BI 78D3 matrix secreting fibroblasts in fibrosis involving vital organs like kidney, liver and lung. With regard to renal fibrosis, one report suggested that proximal tubule epithelial cells contributed to 36% of the total fibroblasts pool through EMT. Although a growing body of evidence from both in vitro and animal studies confirm the occurrence of EMT in renal epithelial cells, the reports from human samples are sparse. In addition to EMT, mesenchymal transition of endothelial cells and bone marrow derived mesenchymal cells have also been shown to contribute to renal fibrosis. Recently, the Duffield group demonstrated pericytes to be the major source of renal interstitial fibroblasts and these results question the validity of EMT as a precursor of interstitial fibroblasts. In fibrotic kidneys the matrix is composed of a number of constituents that include collagen I, collagen III, fibronectin etc. Whether all these matrix proteins are secreted by one fibroblast population or fibroblasts arising from different sources secrete different matrix proteins has not been addressed. One could hypothesise that the origin of fibroblasts is variable depending on the model studied and they could secrete different matrix constituents. The phenotypic transition of epithelial cells involves coordinated involvement of multiple signalling pathways. The loss of Ecadherin and de novo acquisition of a-SMA are considered as important features of phenotype transition process of epithelial cells. Both E-cadherin and a- SMA genes have E-box elements in their promoter region and Ebox binding bHLH proteins like E12 and E47 have been implicated in the regulation of the expression of both of them. Id2 has been shown to prevent the downregulation of Ecadherin in epithelial cell models. In these cell models Id2 was found to suppress a-SMA expression after TGFb1 stimulation- a well characterised profibrotic growth CP 135807 factor and inducer of EMT. TGFb1 regulates the expression of markers of EMT through activating predominantly Smad2/3 signalling in human renal PTEC model. In these cells TGFb1 induced Id1 expression, another member of Id family through Smad2/3 signalling and this resulted in E-cadherin loss. However Id1 upregulation was not involved in TGFb1 induction of a-SMA. In contrast to TGFb1, BMP 7 the other member of TGF family has been shown to have anti-fibrotic effect in both in vivo and in vitro models of renal fibrosis. One of the mechanisms by which BMP 7 exerts its anti-fibrotic effect is by inhibiting TGFb1 mediated E-cadherin loss and subsequent development of EMT at least in murine models. The latter result has not been consistently replicated in human models.