Plasticity of kidney cells: Role in kidney remodeling and scarring

The progression of renal scarring and the associated loss of function remains one of the main challenges in nephrology. Until recently, the glomerular and tubulointerstitial scarring processes were thought to involve primarily interactions between infiltrating inflammatory cells and resident renal cells culminating in loss of renal cells and their replacement by extracellular collagenous matrix (ECM). This review focuses on new aspects of renal response to injury and remodeling. Emphasis is on the plasticity of renal cells with the capacity of both glomerular and tubular cells to assume a range of phenotypes during the remodeling process. Both glomerular and tubular epithelial cells regress to primitive/embryonic mesenchymal phenotype in response to injury. This reverse embryogenesis is a key step in renal healing and scarring. In addition to the plasticity of intrinsic renal cells, it is becoming apparent that renal remodeling in health and disease involves the migration of progenitor hematopoietic stem cells into the kidneys. These cells assume various glomerular and tubular epithelial phenotype. They are also involved in the evolution of lesions toward healing or scarring. A better understanding of some of these key events in renal remodeling and their mediators may open the way to new interventions based on their manipulations and aimed at favoring renal healing and preventing scarring.