Bone marrow mesenchymal stem cells attenuate the progression of focal segmental glomerulosclerosis in rat models
Abstract Background Focal segmental glomerulosclerosis (FSGS) is the most common glomerular etiology of end-stage kidney disease (ESKD). Increasing evidence has indicated the reparative potential of mesenchymal stem cells (MSCs) in damaged diseased kidneys. However, the effect of bone marrow mesench...
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| Format: | Article |
| Language: | English |
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BMC
2018-11-01
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| Series: | BMC Nephrology |
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| Online Access: | http://link.springer.com/article/10.1186/s12882-018-1137-5 |
| _version_ | 1818304709494046720 |
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| author | Ru-chun Yang Xiao-ling Zhu Jun Wang Feng Wan Hua-qin Zhang Yi Lin Xuan-li Tang Bin Zhu |
| author_facet | Ru-chun Yang Xiao-ling Zhu Jun Wang Feng Wan Hua-qin Zhang Yi Lin Xuan-li Tang Bin Zhu |
| author_sort | Ru-chun Yang |
| collection | DOAJ |
| description | Abstract Background Focal segmental glomerulosclerosis (FSGS) is the most common glomerular etiology of end-stage kidney disease (ESKD). Increasing evidence has indicated the reparative potential of mesenchymal stem cells (MSCs) in damaged diseased kidneys. However, the effect of bone marrow mesenchymal stem cells (BMSCs) on the FSGS progression remains unclear. This study aimed to investigate the protective effects of BMSCs on FSGS progression. Methods A rat model of FSGS was generated via unilateral nephrectomy plus adriamycin injection. Rat BMSCs were isolated and characterized on the basis of their differentiative potential towards adipocytes and osteoblasts and via flow cytometry analysis. Thereafter, rat BMSCs were transplanted into FSGS recipients through the caudal vein. After 8 weeks, 24-h proteinuria, serum creatinine, and urea nitrogen levels were determined. Renal morphology was assessed using a light and transmission electron microscope. MMP9 and TIMP-1 positive cells were detected via immunohistochemical analysis. Expression levels of proinflammatory cytokines IL-6 and TNF-α were examined via RT-PCR. Results The isolated adherent cells from the bone marrow of rats were phenotypically and functionally equivalent to typical MSCs. Clinical examination revealed that BMSC transplantation reduced the 24-h urinary protein excretion, and serum creatinine and urea nitrogen levels. Renal morphology was ameliorated in BMSCs-transplanted rats. Mechanistically, BMSC transplantation significantly downregulated TIMP-1 and upregulated MMP9, thereby increasing the renal MMP9/TIMP-1 ratio. Moreover, BMSC transplantation also downregulated IL-6 and TNF-α. Conclusions BMSC transplantation can attenuate FSGS progression in a rat model of FSGS, thereby providing a theoretical foundation for the application of autologous BMSCs in clinical FSGS therapy. |
| first_indexed | 2024-12-13T06:15:00Z |
| format | Article |
| id | doaj.art-d59522f6fcbd452a8305ee9d347ed7c0 |
| institution | Directory Open Access Journal |
| issn | 1471-2369 |
| language | English |
| last_indexed | 2024-12-13T06:15:00Z |
| publishDate | 2018-11-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Nephrology |
| spelling | doaj.art-d59522f6fcbd452a8305ee9d347ed7c02022-12-21T23:56:59ZengBMCBMC Nephrology1471-23692018-11-0119111010.1186/s12882-018-1137-5Bone marrow mesenchymal stem cells attenuate the progression of focal segmental glomerulosclerosis in rat modelsRu-chun Yang0Xiao-ling Zhu1Jun Wang2Feng Wan3Hua-qin Zhang4Yi Lin5Xuan-li Tang6Bin Zhu7Departmgent of Nephrology (Key laboratory of Zhejiang province, management of kidney disease), Hangzhou Hospital of Traditional Chinese MedicineDepartmgent of Nephrology (Key laboratory of Zhejiang province, management of kidney disease), Hangzhou Hospital of Traditional Chinese MedicineDepartmgent of Nephrology (Key laboratory of Zhejiang province, management of kidney disease), Hangzhou Hospital of Traditional Chinese MedicineDepartmgent of Nephrology (Key laboratory of Zhejiang province, management of kidney disease), Hangzhou Hospital of Traditional Chinese MedicineDepartmgent of Nephrology (Key laboratory of Zhejiang province, management of kidney disease), Hangzhou Hospital of Traditional Chinese MedicineDepartmgent of Nephrology (Key laboratory of Zhejiang province, management of kidney disease), Hangzhou Hospital of Traditional Chinese MedicineDepartmgent of Nephrology (Key laboratory of Zhejiang province, management of kidney disease), Hangzhou Hospital of Traditional Chinese MedicineDepartmgent of Nephrology (Key laboratory of Zhejiang province, management of kidney disease), Hangzhou Hospital of Traditional Chinese MedicineAbstract Background Focal segmental glomerulosclerosis (FSGS) is the most common glomerular etiology of end-stage kidney disease (ESKD). Increasing evidence has indicated the reparative potential of mesenchymal stem cells (MSCs) in damaged diseased kidneys. However, the effect of bone marrow mesenchymal stem cells (BMSCs) on the FSGS progression remains unclear. This study aimed to investigate the protective effects of BMSCs on FSGS progression. Methods A rat model of FSGS was generated via unilateral nephrectomy plus adriamycin injection. Rat BMSCs were isolated and characterized on the basis of their differentiative potential towards adipocytes and osteoblasts and via flow cytometry analysis. Thereafter, rat BMSCs were transplanted into FSGS recipients through the caudal vein. After 8 weeks, 24-h proteinuria, serum creatinine, and urea nitrogen levels were determined. Renal morphology was assessed using a light and transmission electron microscope. MMP9 and TIMP-1 positive cells were detected via immunohistochemical analysis. Expression levels of proinflammatory cytokines IL-6 and TNF-α were examined via RT-PCR. Results The isolated adherent cells from the bone marrow of rats were phenotypically and functionally equivalent to typical MSCs. Clinical examination revealed that BMSC transplantation reduced the 24-h urinary protein excretion, and serum creatinine and urea nitrogen levels. Renal morphology was ameliorated in BMSCs-transplanted rats. Mechanistically, BMSC transplantation significantly downregulated TIMP-1 and upregulated MMP9, thereby increasing the renal MMP9/TIMP-1 ratio. Moreover, BMSC transplantation also downregulated IL-6 and TNF-α. Conclusions BMSC transplantation can attenuate FSGS progression in a rat model of FSGS, thereby providing a theoretical foundation for the application of autologous BMSCs in clinical FSGS therapy.http://link.springer.com/article/10.1186/s12882-018-1137-5BMSCFSGSMMP9/TIMP-1Proinflammatory cytokinesRat |
| spellingShingle | Ru-chun Yang Xiao-ling Zhu Jun Wang Feng Wan Hua-qin Zhang Yi Lin Xuan-li Tang Bin Zhu Bone marrow mesenchymal stem cells attenuate the progression of focal segmental glomerulosclerosis in rat models BMC Nephrology BMSC FSGS MMP9/TIMP-1 Proinflammatory cytokines Rat |
| title | Bone marrow mesenchymal stem cells attenuate the progression of focal segmental glomerulosclerosis in rat models |
| title_full | Bone marrow mesenchymal stem cells attenuate the progression of focal segmental glomerulosclerosis in rat models |
| title_fullStr | Bone marrow mesenchymal stem cells attenuate the progression of focal segmental glomerulosclerosis in rat models |
| title_full_unstemmed | Bone marrow mesenchymal stem cells attenuate the progression of focal segmental glomerulosclerosis in rat models |
| title_short | Bone marrow mesenchymal stem cells attenuate the progression of focal segmental glomerulosclerosis in rat models |
| title_sort | bone marrow mesenchymal stem cells attenuate the progression of focal segmental glomerulosclerosis in rat models |
| topic | BMSC FSGS MMP9/TIMP-1 Proinflammatory cytokines Rat |
| url | http://link.springer.com/article/10.1186/s12882-018-1137-5 |
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