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Abstract: TH-PO886

Diabetes Potentiates the Differentiation of Bone Marrow-Derived Cells into Glomerular Endothelium

Session Information

Category: Diabetic Kidney Disease

  • 601 Diabetic Kidney Disease: Basic

Authors

  • Nobuta, Hiroshi, Shiga University Of Medical Science, Otsu, Shiga, Japan
  • Nakagawa, Takahiko, Nara Medical University, Kashihara, Nara, Japan
  • Katagi, Miwako, Shiga University of Medical Science, Otsu , Shiga, Japan
  • Kume, Shinji, Shiga University Of Medical Science, Otsu, Shiga, Japan
  • Terashima, Tomoya, Shiga University of Medical Science, Otsu , Shiga, Japan
  • Kojima, Hideto, Shiga University of Medical Science, Otsu , Shiga, Japan
  • Araki, Shin-ichi, Shiga University Of Medical Science, Otsu, Shiga, Japan
  • Maegawa, Hiroshi, Shiga University Of Medical Science, Otsu, Shiga, Japan
Background

Diabetes causes its complication including neuropathy and nephropathy, and these disorders could share a common mechanism. Recently, it has been shown that bone marrow-derived cells (BMDCs) play a role in the development of diabetic neuropathy. In particular, BMDCs expressing TNF-α reach peripheral neuronal systems to cause functional disorders. However, it remains unclear if BMDCs are involved in the kidney injury of diabetes. We thus hypothesized that BMDCs cause diabetic nephropathy (DN). To test our hypothesis, we examined the role of BMDCs in mice with DN.

Methods

We transplanted the total bone marrow of GFP-Tg mice into wild type mice and then induced diabetes by intraperitoneal injection of 55mg/kg streptozotocin (STZ) for five consecutive days. At 6 and 20 weeks after STZ injection, mice were sacrificed for analyses. Non-diabetic control mice were injected citrate buffer only.

Results

We first confirmed using FACS analysis that over 98% of BMDCs of recipient mice were GFP positive. Immunofluorescence study demonstrated that the number of GFP-positive BMDCs in diabetic glomerulus was significantly higher than that in non-diabetic glomerulus. Most GFP-positive cells were also positive for CD31 and isolectin B4, but negative for podocin ,α8 integrin and F4/80, suggesting BMDCs could differentiate into glomerular endothelial cells. Interestingly, the number of residential endothelial cells (GFP-negative endothelial cells) were identical between diabetic and non-diabetic glomerulus. These data suggest that BMDCs could contribute to the development of neovascularization in DN.

Conclusion

BMDCs arrive at glomerulus and they may be involved in neovascularization in diabetic mice. BMDCs could play a potential role in the development of DN.