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Published on: March 3, 2023
Placenta-derived mesenchymal stem cells protect against diabetic kidney disease by upregulating autophagy-mediated
Honghong Liu1, Jiao Wang1,2,3, Guanru Yue4
1Department of Endocrinology and Metabolism, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, P.R.China.
Abstract:
Diabetic kidney disease (DKD) is a common chronic microvascular complication of diabetes mellitus. Although studies have indicated the therapeutic potential of mesenchymal stem cells (MSCs) for DKD, the underlying molecular mechanisms remain unclear. Herein, we explored the renoprotective effect of placenta-derived MSCs (P-MSCs) and the potential mechanism of SIRT1/FOXO1 pathway-mediated autophagy in DKD. The urine microalbumin/creatinine ratio was determined using ELISA, and renal pathological changes were detected by special staining techniques. Immunofluorescence was used for detecting the renal tissue expression of podocin and nephrin; immunohistochemistry for the renal expression of autophagy-related proteins (LC3, Beclin-1, SIRT1, and FOXO1); and western blotting and PCR for the expression of podocyte autophagy- and pathway-related indicators. We found that P-MSCs ameliorated renal tubular injury and glomerular mesangial matrix deposition and alleviated podocyte damage in DKD rats. PMSCs enhanced autophagy levels and increased SIRT1 and FOXO1 expression in DKD rat renal tissue, whereas the autophagy inhibitor 3-methyladenine significantly attenuated the renoprotective effect of P-MSCs. P-MSCs improved HG-induced Mouse podocyte clone5(MPC5)injury, increased podocyte autophagy, and upregulated SIRT1 and FOXO1 expression. Moreover, downregulation of SIRT1 expression blocked the P-MSC-mediated enhancement of podocyte autophagy and improvement of podocyte injury. Thus, P-MSCs can significantly improve renal damage and reduce podocyte injury in DKD rats by modulating the SIRT1/FOXO1 pathway and enhancing podocyte autophagy.
Insights
Placenta-derived mesenchymal stem cells (P-MSCs) protect against diabetic kidney disease (DKD) by enhancing podocyte autophagy via the SIRT1/FOXO1 pathway. This study clarifies the mechanism behind P-MSC therapy for DKD.
Area of Science:
- Nephrology
- Stem Cell Therapy
- Molecular Mechanisms
Background:
- Diabetic kidney disease (DKD) is a major complication of diabetes, and its molecular mechanisms are not fully understood.
- Mesenchymal stem cells (MSCs) show therapeutic potential for DKD, but the underlying pathways require elucidation.
- Placenta-derived MSCs (P-MSCs) are being investigated for their effects on DKD.
Purpose of the Study:
- To explore the renoprotective effects of P-MSCs in a rat model of DKD.
- To investigate the potential mechanism involving the SIRT1/FOXO1 pathway and autophagy in P-MSC-mediated DKD treatment.
- To assess the impact of P-MSCs on podocyte injury and function in DKD.
Main Methods:
- DKD rat models were treated with P-MSCs.
- Renal function and pathology were assessed using biochemical assays (urine microalbumin/creatinine ratio) and histological staining.
- Protein and gene expression related to podocyte injury, autophagy (LC3, Beclin-1), and the SIRT1/FOXO1 pathway were analyzed via immunofluorescence, immunohistochemistry, western blotting, and PCR.
Main Results:
- P-MSCs ameliorated renal tubular injury, glomerular mesangial matrix deposition, and podocyte damage in DKD rats.
- P-MSCs enhanced autophagy and upregulated SIRT1 and FOXO1 expression in renal tissues.
- Inhibition of autophagy or SIRT1 expression attenuated the renoprotective effects of P-MSCs, indicating their crucial role.
Conclusions:
- P-MSCs exert significant renoprotective effects in DKD by improving renal and podocyte injury.
- The mechanism involves the modulation of the SIRT1/FOXO1 pathway, leading to enhanced podocyte autophagy.
- P-MSC therapy holds promise for treating DKD through this specific molecular pathway.
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