Transforming growth factor-Β and kidney dysfunction

In addition to their critical role in embryogenesis of the kidney, members of the transforming growth factor (TGF)-Β superfamily direct a number of pathways important in the maintenance of homeostasis in the differentiated kidney. TGF-Β family members also play an important role in cell-cycle regulation. Through induction of cyclin-dependent kinase inhibitors, TGF-Β promotes a hypertrophic response of renal tubular epithelial cells and glomerular mesangial cells. This TGF-Β driven hypertrophic response, which occurs in diabetic nephropathy, may have deleterious effects on the kidney. In contrast, many human cancers are associated with loss of the growth inhibitory effects of TGF-Β. TGF-Β may promote or inhibit inflammation, an outcome which appears to depend on the cell type(s) involved and on potential interactions with other signaling pathways that regulate inflammatory responses. In recent studies, TGF-Β has been implicated as a key mediator of the epithelial to mesenchymal transition, a process through which epithelial cells acquire characteristics of myofibroblasts which synthesize and deposit extracellular matrix macromolecules and lead to the development of fibrosis, a characteristic feature of chronic renal disease irrespective of etiology. In this brief overview, we highlight recent advances in our understanding of TGF-Β signaling that contribute to the development and progression of chronic renal disease.