Transdifferentiation of epithelial glomerular cells.

Cell transdifferentiation is characterized by loss of some phenotypes along with acquisition of new phenotypes in differentiated cells. Differentiated cells are endowed with the capacity of transforming into cells of a different type having other functions (1,2). Gene expression in differentiated cells has long been considered an irreversible phenomenon that is established at the time of replication. Given that, although repressed, the same genetic framework is present in all cell types, a change in gene expression among differentiated cells was predictable in particular conditions. In fact, the differentiated state of a given cell is not irreversible. It depends on the upand downregulation exerted by specific molecules (3,4). Apart from organogenesis, malignant cell development, and tumor progression, the best documented examples of cell transdifferentiation concern transdifferentiation of epithelial cells into mesenchymatous cells (EMT). Such a transdifferentiation of epithelial cells into myofibroblasts has been identified as a factor fostering fibrosis in various organs such as the liver (5,6), the lung (7), and the kidney (8,9). Myofibroblasts exhibit features common to both fibroblasts and myocytes and may be considered as activated fibroblasts that express -smooth muscle actin ( -SMA) (10). Their ability to proliferate and to synthesize extracellular matrix (interstitial type collagens) is remarkable (7,11,12). In the human kidney, we have been the first to describe transdifferentiation of glomerular epithelial cells into myofibroblastic or into macrophagic cells (13–15).