Calpain-10 drives podocyte apoptosis and renal injury in diabetic nephropathy
Tao Wang,1 Yanbin Gao,1,2 Xiaolei Wang,1 Yimin Shi,1 Jiayi Xu,1 Bingjie Wu,1 Jiaxin He,1 Yimeng Li2 1School of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of China; 2Beijing Key Laboratory of TCM Collateral Disease Theory Research, Beijing, People&a...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2019-09-01
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| Series: | Diabetes, Metabolic Syndrome and Obesity |
| Subjects: | |
| Online Access: | https://www.dovepress.com/calpain-10-drives-podocyte-apoptosis-and-renal-injury-in-diabetic-neph-peer-reviewed-article-DMSO |
| _version_ | 1811173894876299264 |
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| author | Wang T Gao Y Wang X Shi Y Xu J Wu B He J Li Y |
| author_facet | Wang T Gao Y Wang X Shi Y Xu J Wu B He J Li Y |
| author_sort | Wang T |
| collection | DOAJ |
| description | Tao Wang,1 Yanbin Gao,1,2 Xiaolei Wang,1 Yimin Shi,1 Jiayi Xu,1 Bingjie Wu,1 Jiaxin He,1 Yimeng Li2 1School of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of China; 2Beijing Key Laboratory of TCM Collateral Disease Theory Research, Beijing, People’s Republic of ChinaCorrespondence: Yanbin GaoSchool of Traditional Chinese Medicine, Capital Medical University, No. 10, Youanmenwai, Xitoutiao, Fengtai District, Beijing 100069, People’s Republic of ChinaTel +86 108 391 1720Email dfyynfm@163.comBackground: Diabetic nephropathy (DN) is a progressive microvascular complication of diabetes mellitus (DM), driven largely by podocyte apoptosis. The cysteine protease Calpain 10 is known to augment apoptosis and necrosis, and is a potential therapeutic target in DN.Methods: Type 2 diabetes was induced in SD rats by high-fat diet (HFD) feeding and streptozotocin (STZ) injections, and simulated in vitro by culturing conditionally immortalized mouse podocytes in hyperlipidemic (PA, 100 μM) conditions. The rate of apoptosis in the renal tissues and cultured podocytes was determined by TUNEL assay. The expression of Calpain 10 and its biological effects were assayed by real-time PCR, Western blotting, immunofluorescence and electron microscopy.Results: Calpain 10 was up-regulated in the kidneys of DN rats, as well as immortalized mouse podocytes. High levels of Calpain 10 was associated with renal dysfunction and tissue destruction, and podocyte injury and apoptosis. Knockdown of Calpain 10 protected podocytes by decreasing apoptosis rate, and upregulated nephrin.Conclusion: Calpain 10 is a pro-apoptotic factor in DN, and can be targeted for treating glomerular diseases.Keywords: Calpain 10, podocyte, apoptosis, diabetic nephropathy |
| first_indexed | 2024-04-10T17:55:27Z |
| format | Article |
| id | doaj.art-c08efc1cb26446f9b36f80fa7205a41b |
| institution | Directory Open Access Journal |
| issn | 1178-7007 |
| language | English |
| last_indexed | 2024-04-10T17:55:27Z |
| publishDate | 2019-09-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Diabetes, Metabolic Syndrome and Obesity |
| spelling | doaj.art-c08efc1cb26446f9b36f80fa7205a41b2023-02-02T19:00:34ZengDove Medical PressDiabetes, Metabolic Syndrome and Obesity1178-70072019-09-01Volume 121811182048529Calpain-10 drives podocyte apoptosis and renal injury in diabetic nephropathyWang TGao YWang XShi YXu JWu BHe JLi YTao Wang,1 Yanbin Gao,1,2 Xiaolei Wang,1 Yimin Shi,1 Jiayi Xu,1 Bingjie Wu,1 Jiaxin He,1 Yimeng Li2 1School of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of China; 2Beijing Key Laboratory of TCM Collateral Disease Theory Research, Beijing, People’s Republic of ChinaCorrespondence: Yanbin GaoSchool of Traditional Chinese Medicine, Capital Medical University, No. 10, Youanmenwai, Xitoutiao, Fengtai District, Beijing 100069, People’s Republic of ChinaTel +86 108 391 1720Email dfyynfm@163.comBackground: Diabetic nephropathy (DN) is a progressive microvascular complication of diabetes mellitus (DM), driven largely by podocyte apoptosis. The cysteine protease Calpain 10 is known to augment apoptosis and necrosis, and is a potential therapeutic target in DN.Methods: Type 2 diabetes was induced in SD rats by high-fat diet (HFD) feeding and streptozotocin (STZ) injections, and simulated in vitro by culturing conditionally immortalized mouse podocytes in hyperlipidemic (PA, 100 μM) conditions. The rate of apoptosis in the renal tissues and cultured podocytes was determined by TUNEL assay. The expression of Calpain 10 and its biological effects were assayed by real-time PCR, Western blotting, immunofluorescence and electron microscopy.Results: Calpain 10 was up-regulated in the kidneys of DN rats, as well as immortalized mouse podocytes. High levels of Calpain 10 was associated with renal dysfunction and tissue destruction, and podocyte injury and apoptosis. Knockdown of Calpain 10 protected podocytes by decreasing apoptosis rate, and upregulated nephrin.Conclusion: Calpain 10 is a pro-apoptotic factor in DN, and can be targeted for treating glomerular diseases.Keywords: Calpain 10, podocyte, apoptosis, diabetic nephropathyhttps://www.dovepress.com/calpain-10-drives-podocyte-apoptosis-and-renal-injury-in-diabetic-neph-peer-reviewed-article-DMSOCalpain 10podocyteapoptosisdiabetic nephropathy |
| spellingShingle | Wang T Gao Y Wang X Shi Y Xu J Wu B He J Li Y Calpain-10 drives podocyte apoptosis and renal injury in diabetic nephropathy Diabetes, Metabolic Syndrome and Obesity Calpain 10 podocyte apoptosis diabetic nephropathy |
| title | Calpain-10 drives podocyte apoptosis and renal injury in diabetic nephropathy |
| title_full | Calpain-10 drives podocyte apoptosis and renal injury in diabetic nephropathy |
| title_fullStr | Calpain-10 drives podocyte apoptosis and renal injury in diabetic nephropathy |
| title_full_unstemmed | Calpain-10 drives podocyte apoptosis and renal injury in diabetic nephropathy |
| title_short | Calpain-10 drives podocyte apoptosis and renal injury in diabetic nephropathy |
| title_sort | calpain 10 drives podocyte apoptosis and renal injury in diabetic nephropathy |
| topic | Calpain 10 podocyte apoptosis diabetic nephropathy |
| url | https://www.dovepress.com/calpain-10-drives-podocyte-apoptosis-and-renal-injury-in-diabetic-neph-peer-reviewed-article-DMSO |
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