The role of Ferritin trafficking in the iron homeostasis of the glomerulus

The kidney plays a major role in systemic iron homeostasis, as it controls the most iron consuming pathway of the body, erythropoiesis. Nevertheless, little is known on iron transport and its regulation in the kidney. Ferritin, the main intracellular iron storage protein, is secreted avidly and taken up by the human transferrin receptor 1. This led us to hypothesize that ferritin may function as an iron transporter, also in the kidney.

To better understand iron homeostasis of the kidney, we decided to focus first on the glomerulus, and test if secretion and re-uptake of ferritin by specific glomerular cell types affects the iron distribution between kidney-cells, and how this may change cellular iron status.

We isolate glomeruli from mouse-kidneys and grow primary cultures of podocytes and mesangial cells, for analysis of secretion and uptake of ferritin. To find the ferritin location in whole tissue, we co-localize ferritin and glomerular cell-markers in kidney sections and isolated glomeruli.

Following iron injections, the renal distribution of ferric iron is dynamic for several days. In addition, the two ferritin subunits H and L are distributed differently across sections of iron-overloaded mice.

The staining results suggested, that glomerular endothelial cells contain very little ferritin, while ferritin expression is more prominent in podocyte and mesangial cells. The ability to grow primary cultures of podocyte and mesangial cells will be a useful tool to analyze their ferritin expression, secretion and uptake.