Placenta-derived mesenchymal stem cells protect against diabetic kidney disease by upregulating autophagy-mediated SIRT1/FOXO1 pathway
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...
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Taylor & Francis Group
2024-12-01
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| Series: | Renal Failure |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/0886022X.2024.2303396 |
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| author | Honghong Liu Jiao Wang Guanru Yue Jixiong Xu |
| author_facet | Honghong Liu Jiao Wang Guanru Yue Jixiong Xu |
| author_sort | Honghong Liu |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-8b496807dbb442fc9453ecd5d09a7e6c |
| institution | Kabale University |
| issn | 0886-022X 1525-6049 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
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| series | Renal Failure |
| spelling | doaj-art-8b496807dbb442fc9453ecd5d09a7e6c2025-01-23T04:17:49ZengTaylor & Francis GroupRenal Failure0886-022X1525-60492024-12-0146110.1080/0886022X.2024.2303396Placenta-derived mesenchymal stem cells protect against diabetic kidney disease by upregulating autophagy-mediated SIRT1/FOXO1 pathwayHonghong Liu0Jiao Wang1Guanru Yue2Jixiong Xu3Department of Endocrinology and Metabolism, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, P.R. ChinaDepartment of Endocrinology and Metabolism, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, P.R. ChinaDepartment of Medical Genetics and Cell biology, Medical College of Nanchang University, Nanchang, P.R. ChinaDepartment of Endocrinology and Metabolism, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, P.R. ChinaDiabetic 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.https://www.tandfonline.com/doi/10.1080/0886022X.2024.2303396Placenta-derived mesenchymal stem cellsautophagydiabetic kidney diseaseSIRT1/FOXO1 pathwaypodocyte injury |
| spellingShingle | Honghong Liu Jiao Wang Guanru Yue Jixiong Xu Placenta-derived mesenchymal stem cells protect against diabetic kidney disease by upregulating autophagy-mediated SIRT1/FOXO1 pathway Renal Failure Placenta-derived mesenchymal stem cells autophagy diabetic kidney disease SIRT1/FOXO1 pathway podocyte injury |
| title | Placenta-derived mesenchymal stem cells protect against diabetic kidney disease by upregulating autophagy-mediated SIRT1/FOXO1 pathway |
| title_full | Placenta-derived mesenchymal stem cells protect against diabetic kidney disease by upregulating autophagy-mediated SIRT1/FOXO1 pathway |
| title_fullStr | Placenta-derived mesenchymal stem cells protect against diabetic kidney disease by upregulating autophagy-mediated SIRT1/FOXO1 pathway |
| title_full_unstemmed | Placenta-derived mesenchymal stem cells protect against diabetic kidney disease by upregulating autophagy-mediated SIRT1/FOXO1 pathway |
| title_short | Placenta-derived mesenchymal stem cells protect against diabetic kidney disease by upregulating autophagy-mediated SIRT1/FOXO1 pathway |
| title_sort | placenta derived mesenchymal stem cells protect against diabetic kidney disease by upregulating autophagy mediated sirt1 foxo1 pathway |
| topic | Placenta-derived mesenchymal stem cells autophagy diabetic kidney disease SIRT1/FOXO1 pathway podocyte injury |
| url | https://www.tandfonline.com/doi/10.1080/0886022X.2024.2303396 |
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