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Updated: Jan 22, 2026
Isolation, Characterization, And High Throughput Extracellular Flux Analysis of Mouse Primary Renal Tubular Epithelial Cells
Published on: June 20, 2018
Mesenchymal stem cells prevent the progression of diabetic nephropathy by improving mitochondrial function in tubular
Seung Eun Lee1,2,3, Jung Eun Jang1,2,4, Hyun Sik Kim2
1Department of Internal Medicine, University of Ulsan College of Medicine, Seoul, Korea.
Abstract:
The administration of mesenchymal stem cells (MSCs) was shown to attenuate overt as well as early diabetic nephropathy in rodents, but the underlying mechanism of this beneficial effect is largely unknown. Inflammation and mitochondrial dysfunction are major pathogenic factors in diabetic nephropathy. In this study, we found that the repeated administration of MSCs prevents albuminuria and injury to tubular epithelial cells (TECs), an important element in the progression of diabetic nephropathy, by improving mitochondrial function. The expression of M1 macrophage markers was significantly increased in diabetic kidneys compared with that in control kidneys. Interestingly, the expression of arginase-1 (Arg1), an important M2 macrophage marker, was reduced in diabetic kidneys and increased by MSC treatment. In cultured TECs, conditioned media from lipopolysaccharide-activated macrophages reduced peroxisomal proliferator-activated receptor gamma coactivator 1α (Pgc1a) expression and impaired mitochondrial function. The coculture of macrophages with MSCs increased and decreased the expression of Arg1 and M1 markers, respectively. Treatment with conditioned media from cocultured macrophages prevented activated macrophage-induced mitochondrial dysfunction in TECs. In the absence of MSC coculture, Arg1 overexpression in macrophages reversed Pgc1a suppression in TECs. These observations suggest that MSCs prevent the progression of diabetic nephropathy by reversing mitochondrial dysfunction in TECs via the induction of Arg1 in macrophages.
Insights
Mesenchymal stem cells (MSCs) protect against diabetic kidney disease by improving mitochondrial function in kidney cells. MSCs achieve this by promoting macrophages to express arginase-1 (Arg1), which reverses mitochondrial dysfunction.
Area of Science:
- Nephrology
- Stem Cell Biology
- Immunology
Background:
- Diabetic nephropathy (DN) is a major complication of diabetes, characterized by inflammation and mitochondrial dysfunction.
- Mesenchymal stem cells (MSCs) show therapeutic potential in DN, but their mechanisms remain unclear.
- Inflammation and impaired mitochondrial function in tubular epithelial cells (TECs) drive DN progression.
Purpose of the Study:
- To elucidate the mechanism by which MSCs attenuate diabetic nephropathy.
- To investigate the role of macrophage polarization and mitochondrial function in MSC-mediated protection.
Main Methods:
- Rodent models of diabetic nephropathy were treated with MSCs.
- Macrophage polarization markers (M1 and M2) and arginase-1 (Arg1) expression were analyzed.
- In vitro studies involved co-culturing TECs with activated macrophages and MSCs.
- Mitochondrial function and Pgc1a expression in TECs were assessed.
Main Results:
- MSC treatment prevented albuminuria and TEC injury in diabetic rodents.
- MSCs increased Arg1 expression and decreased M1 markers in kidney macrophages.
- Conditioned media from MSC-macrophage co-cultures protected TECs from mitochondrial dysfunction.
- Arg1 overexpression in macrophages reversed lipopolysaccharide-induced Pgc1a suppression and mitochondrial dysfunction in TECs.
Conclusions:
- MSCs ameliorate diabetic nephropathy by restoring mitochondrial function in TECs.
- This protective effect is mediated by MSC-induced Arg1 expression in macrophages.
- Targeting macrophage polarization represents a potential therapeutic strategy for diabetic nephropathy.
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