Altered dynamics in the renal lymphatic circulation of type 1 and type 2 diabetic mice.

The dynamics of the renal lymphatic circulation in diabetic nephropathy is not fully elucidated. The present study evaluated the effect of diabetic nephropathy on the renal lymphatic circulation in streptozotocin (STZ)-induced type 1 diabetic mice (ICR-STZ) and in type 2 diabetic KK/Ta mice which were fed a high fat diet (KK/Ta-HF). The diabetic mouse kidneys developed edema because of the nephropathy. In control mice renal lymphatic vessels distributed in the cortex but rarely in the medulla while in ICR-STZ and KK/Ta-HF mice, there were many lymphatic vessels with small lumen in both cortex and medulla. Total numbers and areas of renal blood vessels in the diabetic mice were similar to those in the controls while the total numbers and areas of renal lymphatic vessels were larger in diabetic mice than in the controls. There were statistically significant differences in the numbers of lymphatic vessels with diameters of 50-100 µm between the ICR-STZ and the control ICR mice, and in the numbers of lymphatic capillaries with diameters smaller than 50 µm between the KK/Ta-HF and the control KK/Ta mice. The diabetic nephropathy may induce the lymphangiogenesis or result in at least the renal lymphatic vessel expansion.

Expression of Toll-Like Receptor 4 in Glomerular Endothelial Cells under Diabetic Conditions.

Diabetic conditions promote glomerulosclerosis by mesangial cells but the mechanisms are not fully elucidated. The present study evaluated the expression of toll-like receptor 4 in glomerular endothelial cells in the streptozotocin (STZ)-induced type 1 diabetic mouse (ICR-STZ) and the type 2 diabetic KK/TaJcl mouse which were fed a high fat diet feed (KK/Ta-HF). In the ICR-STZ and KK/Ta-HF almost glomeruli were immunostained with anti-TLR4 but there was no glomerulus immunostained by ani-TLR4 in the control ICR and KK/Ta. Laser-scanning confocal microscopy showed that the TLR4-positive region did not coincide with the podoplanin-positive region but coincide with the PECAM-1- and VE-cadherin-positive regions in the glomeruli of the ICR-STZ and KK/Ta-HF. The in situ hybridization showed that almost signals for TLR4 mRNA were present in the glomerulus of the ICR-STZ and KK/Ta-HF to a stronger extent than in the control ICR and KK/Ta. These suggest that glomerular endothelial cells usually express the TLR4 gene and hyperglycemia in the diabetic condition induces the TLR4 protein expression in the glomerular capillary endothelial cells. Cytokine productions through the TLR signaling pathway in glomerular endothelial cells may allow mesangial cells to produce extracellular matrix proteins in the diabetic milieu.