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Mesangial Injury and Capillary Ballooning Precede Podocyte Damage in Nephrosclerosis

Published:September 20, 2022DOI:https://doi.org/10.1016/j.ajpath.2022.08.007

      Abstract

      The development of focal and segmental glomerulosclerosis (FSGS) in consequence of glomerular hypertension due to arterial hypertension is widely considered as a podocyte disease. However, the primary damage is encountered in the mesangium. Mesangial cells, in acute settings, disconnect from their insertions to the glomerular basement membrane (GBM) causing a ballooning of capillaries and severe changes of the folding pattern of the GBM, of the arrangement of the capillaries and thus of the architecture of the tuft. The displacements of capillaries lead to contacts of podocytes to parietal epithelial cells (PECs) initiating the formation of tuft adhesions to Bowman’s capsule (BC), the committed lesion to progress to FSGS. In addition, the displacement of capillaries also causes an abnormal stretching of podocytes resulting in podocyte damage. Thus, the damage of podocytes that starts the sequence to FSGS develops secondarily to the mesangial damage. This sequence was found in two hypertensive rat models of FSGS and in human hypertensive nephrosclerosis.

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