Epithelial-Mesenchymal Transition and Podocyte Loss in Diabetic Kidney Disease

(Top panel) Arrow demarks the epithelial-mesenchymal transition (EMT) in columnar epithelial cells characterized by the presence of tight junctions (TJ) and adherens junctions (AJ) at their apical aspect and adherence to the glomerular basement membrane (GBM) at the basal aspect. Columnar epithelial cells lose cell-cell junctions and their cobblestone morphology and develop a spindle shape, permitting increased motility and promoting migration into and through a degenerating GBM. (Bottom panel) Phenotype change in podocytes. Arborized podocytes have interdigitating foot processes linked by slit diaphragms (SD), but retain more mesenchymal characteristics at baseline, with spindle-shaped processes and expression of vimentin. In diabetic nephropathy, podocytes become effaced and have increased expression of mesenchymal markers. They do not invade the GBM, but rather increased motility results in detachment and loss of podocytes. Abbreviations: α-SMA, α smooth muscle actin; FSP-1, fibroblast-specific protein 1; ILK, integrin-linked kinase; ZO-1, zonula occludens 1.