The histologic disorders and underlying mechanisms of podocytes during diabetes

Abstract

Abstract Diabetic kidney disease (DKD), one of the most common chronic microvascular complications in diabetes mellitus (DM), is the leading cause of chronic kidney disease (CKD) and end-stage renal disease (ESRD) worldwide. The proteinuria in DKD is tightly related to dysmorphology of podocytes including hypertrophy, foot process widening along with its effacement, and ultimately the loss of podocytes. The maintenance of a normal slit diaphragm, actin cytoskeleton, electric charge of the podocyte, and the interplay between podocyte and glomerular basement membrane (GBM) is essential for the podocyte process’s morphology. And the mitotic catastrophe (MC), epithelial-mesenchymal transition, detachment, and apoptosis of podocyte account for the decreased density of podocytes in DKD. From the angle of signaling pathway, several routes including the renin-angiotensin system, insulin signaling, cyclooxygenases (COX) and prostanoids, and notch signaling are proven to play critical roles in podocyte disorders. In this review, we highlight the main histologic abnormalities of podocytes in DKD and focus on their underlying mechanisms.