A causal role for bone marrow-derived cells in diabetic nephropathy

What is it about?

Diabetes induces its complications, including nephropathy and neuropathy. These diseases may share a common mechanism. We previously demonstrated that bone marrow-derived cells (BMDCs) were functionally impaired by diabetic condition to express TNF-α and to cause diabetic neuropathy. This data let us to hypothesize that BMDCs exposed to diabetic condition play a causal role in the development of renal disease. In order to monitor BMDCs, we transplanted total bone marrow from transgenic mice expressing green fluorescent protein (GFP) into irradiated recipient mice in which we induced type 1 diabetes with streptozotocin. We found that the number of BMDCs was higher in glomerulus of diabetic mice compared to that of nondiabetic mice. Interestingly, most of glomerular BMDCs were likely endothelial cells, but not podocyte, mesangial cell, and macrophage. Next, to further confirm the causal role of BMDCs, the total bone marrow of diabetic GFP transgenic mice was transplanted into nondiabetic mice. The result showed that glomerular BMDCs were positively associated with glomerular capillary area in the recipient mice. These cells were also associated with renal injury manifested by albuminuria and mesangial expansion although their blood glucose level was normal. Some of glomerular BMDCs expressed TNF-α, indicating that these cells could initiate kidney disease without hyperglycemia. Finally, endothelial nitric oxide synthase deficient mice failed to attract BMDCs, suggesting that residential endothelial injury was not a cause for the BMDCs accumulation into glomerulus. In summary, this study suggests BMDCs could be involved in the development of diabetic nephropathy.

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Why is it important?

Diabetic nephropathy is a leading cause of end-stage renal disease. However, the precise mechanism remains unclear. This study demonstrated that the bone marrow-derived cells are functionally impaired to express TNF-α by diabetic condition and spread into kidney, in particularly into glomerulus. Interestingly, those cells also exhibit endothelial phenotype. Perhaps, diabetic bone-marrow derived cells would play a key role in the development of diabetic nephropathy.

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