A role for bone marrow-derived cells in diabetic nephropathy

Area of Science:

• Nephrology
• Endocrinology
• Immunology

Background:

• Diabetes mellitus is a systemic disorder with significant renal complications.
• Previous research linked diabetic bone marrow-derived cells (BMDCs) to neuropathy via TNF-α expression.

Purpose of the Study:

• To investigate the role of abnormal BMDCs in the development of diabetic nephropathy.
• To determine if diabetic BMDCs can independently cause glomerular injury.

Main Methods:

• Utilized streptozotocin-induced diabetes in mice with green fluorescent protein-labeled bone marrow transplants.
• Employed confocal microscopy to track BMDC infiltration and phenotype in glomeruli.
• Performed bone marrow transplantation from diabetic to nondiabetic mice.

Main Results:

• Diabetic glomeruli showed increased BMDC infiltration, primarily with endothelial phenotypes.
• Transplantation of diabetic BM into nondiabetic recipients induced albuminuria and mesangial expansion.
• Diabetic BMDCs in recipient glomeruli expressed TNF-α, suggesting a direct pathogenic role.

Conclusions:

• Diabetic BMDCs can initiate glomerular disease independently.
• BMDC infiltration and TNF-α expression are key mechanisms in diabetic nephropathy.
• Resident endothelial dysfunction does not appear to attract BMDCs into the diabetic glomerulus.