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Updated: May 3, 2026

Comparative Proteomic Analysis of Whole Kidney, Medulla, and Cortical Tubules in Diabetic Pathogenesis of Kidney Injury in Mice
Published on: May 2, 2025
Comparison of multipotency and molecular profile of MSCs between CKD and healthy rats
Akifumi Yamada1, Takashi Yokoo, Shinya Yokote
1Project Laboratory for Kidney Regeneration, Institute of DNA Medicine, The Jikei University School of Medicine, Tokyo, Japan.
Abstract:
We previously showed that mesenchymal stem cells (MSCs) can differentiate into a functional miniature kidney, suggesting that MSCs may be a cell source for kidney regeneration. However, MSCs from long-term dialysis patients, which have been exposed to uremic toxin, can exhibit reduced viability. Therefore, the aim of this study was to examine the gene expression profiles and differentiation capabilities of bone marrow- and adipose-derived MSCs from chronic kidney disease (CKD) model rats. CKD was induced in rats by adenine feeding, and then MSCs were isolated from bone marrow (BMSCs) and adipose tissue (ASCs). After confirming MSC surface marker expression, comprehensive gene expression profiles were obtained by RT-PCR array. MSCs were differentiated into adipocytes, osteoblasts, and chondrocytes, and histological and/or functional assays were performed. Tgfb3 expression was up-regulated, while Bmp6, Gdf15, Mmp2, and Vegfa were down-regulated in CKD-ASCs compared with Control-ASCs. There were no significant differences in the gene expression of stemness markers, and the morphology of cells that underwent adipogenesis, osteogenesis, and chondrogenesis, or GPDH activity between CKD and control groups. Comparing BMSCs with ASCs, gene expression of Bglap, Bmp4, Igf1, Itgax, Pparg, Ptprc, and Tnf were up-regulated, while Col1a1, Mmp2, Sox9, and Vegfa were down-regulated in both CKD and control groups. Uremic toxin in CKD rats had a small effect on the gene expression and differentiation of MSCs. However, long-term exposure to uremic toxin and the differences in gene expression of MSCs derived from bone marrow or adipose tissue may affect renal regeneration.
Insights
Mesenchymal stem cells (MSCs) show potential for kidney regeneration. This study found that while uremic toxins had minor effects on MSC gene expression and differentiation, differences between bone marrow and adipose-derived MSCs may impact renal regeneration.
Area of Science:
- Regenerative Medicine
- Stem Cell Biology
- Nephrology
Background:
- Mesenchymal stem cells (MSCs) show promise for kidney regeneration due to their differentiation potential.
- However, uremic toxins from chronic kidney disease (CKD) may impair MSC viability and function.
- Understanding MSC behavior in CKD is crucial for developing effective regenerative therapies.
Purpose of the Study:
- To investigate the gene expression profiles and differentiation capabilities of bone marrow-derived MSCs (BMSCs) and adipose-derived MSCs (ASCs) from CKD model rats.
- To assess the impact of uremic toxins on MSCs.
- To compare MSCs from CKD rats with those from control rats.
Main Methods:
- CKD was induced in rats using adenine feeding.
- MSCs were isolated from bone marrow and adipose tissue.
- RT-PCR arrays were used for gene expression profiling.
- MSCs were differentiated into adipocytes, osteoblasts, and chondrocytes, followed by histological and functional assays.
Main Results:
- CKD-ASCs showed up-regulated Tgfb3 and down-regulated Bmp6, Gdf15, Mmp2, and Vegfa compared to controls.
- No significant differences were observed in stemness markers or differentiation capacity (adipogenesis, osteogenesis, chondrogenesis) between CKD and control MSCs.
- BMSCs and ASCs exhibited distinct gene expression patterns, with several genes up- or down-regulated in both CKD and control groups.
Conclusions:
- Uremic toxins in CKD rats had a limited effect on MSC gene expression and differentiation.
- Differences in gene expression between BMSCs and ASCs exist.
- Long-term uremic toxin exposure and inherent MSC source differences may influence their potential for renal regeneration.

