Occurrence of fenestral diaphragms and knots in renal glomerular endothelia of diabetic mutant MafA−/−MafK+ mice as revealed in embedment‐free transmission electron microscopy

Abstract

Using the advantages (high contrast and transparency and efficient 3D viewing) of embedment-free section transmission electron microscopy (TEM), the occurrence of numerous fenestral diaphragms was clearly shown in 3D en-face viewing of the renal glomerular capillary endothelium of severe overt diabetes mellitus mice, which were generally MafA-deficient and simultaneously MafK-overexpressed specifically in pancreatic β-cells. This presents another example of nephritis-induced diaphragmed fenestrae in the renal glomerular endothelium. In addition, knot-/umbilicus-like structures discrete from and larger than the central knots of regular diaphragms of fenestrated endothelium were clearly demonstrated to occur randomly in the renal glomerular endothelial fenestrae of mutant mice and wild ones. The knot-structures were revealed to be protrusions of underlining basement lamina in conventional TEM by section-tilting observation.

Loss of filtration function in diabetic glomeruli is associated with ultrastructural changes in glomerular endothelial cell fenestrations

“…We observed significantly increased diaphragmed fenestrations in diabetic mice in agreement with the findings of a previous study. 24 Furthermore, we identified increased glomerular PV1, the only known component of diaphragms, expression in diabetic mice and humans. We also observed increased GEnC fenestration width in diaphragmed fenestrations compared to open fenestrations suggesting diaphragms develop in widening GEnC fenestrations.…”

The unique structural and functional characteristics of glomerular endothelial cell fenestrations and their potential as a therapeutic target in kidney disease

“…The number of diaphragmed fenestrae is approximately four times greater in GEnCs recovering from injury ( 12 ). The presence of increased numbers of diaphragmed fenestrations has also been reported in diabetic mice, suggesting pathological injury ( 20 ). Diaphragmed fenestrae are present in the later embryonic stages of GEnC ( 12 , 19 ) and LSEC ( 21 ) development but are lost within 2 wk of birth in rat kidneys ( 22 ).…”