Phenotypic transitions and fibrosis in diabetic nephropathy

Abstract

The cause of renal fibrosis in diabetic nephropathy is widely believed to be phenotypic switching of fibroblasts to an activated state. However, emerging evidence suggests that diabetes also alters the phenotype of normal, non-fibroblast kidney cells, such as mesangial cells, tubular epithelial cells, and bone marrow-derived progenitors. Experiments have shown that cytokines, high glucose, and advanced glycation end products induce profibrotic changes in kidney cell phenotype by the processes of myofibroblast transdifferentiation and epithelial-mesenchymal transition. As a result, differentiated kidney cells become reprogrammed to secrete and accumulate extracellular matrix. This revised view implies that inhibiting phenotypic transitions in nonfibroblasts might limit fibrosis in diabetic nephropathy.