Proto-Oncogene Ets-1 and the Kidney

Most forms of advanced glomerular diseases, if not all, are characterized by abnormal turnover of extracellular matrix (ECM) proteins in glomeruli, resulting in structural alterations of glomerular basement membrane and mesangial matrix, usually leading to proteinuria. It is, therefore, important to elucidate the regulatory mechanisms of ECM metabolism in glomerular diseases. Various types of collagens, laminin, fibronectin, and sulfated proteoglycans are the normal components of glomerular matrix [1– 5]. In vivo and in vitro studies have shown that these matrix components are produced by mesangial and visceral epithelial cells [6, 7]. It has also been demonstrated that in glomerular diseases, phenotypically altered activated renal cells are mainly responsible for the increased production of these matrix components as well as diseasespecific matrix components that are not expressed in the normal kidney [8–11]. Several lines of evidence now suggest that an imbalance between synthesis and degradation of these matrix components is closely associated with accumulation of ECM and subsequent progression of renal diseases [12]. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) have been reported to play an important role in ECM remodeling in various renal diseases [13, 14]. Recent studies have also shown that the proto-oncogene Ets-1 plays a role in the transcriptional regulation of matrix proteinases such as MMP-3 and u-PA [15–19]. We summarize herein the existing information about possible roles of Ets-1 in matrix remodeling as well as other functions in renal diseases.