Hyperoside pre-treatment prevents glomerular basement membrane damage in diabetic nephropathy by inhibiting podocyte heparanase expression
Abstract Glomerular basement membrane (GBM) damage plays a pivotal role in pathogenesis of albuminuria in diabetic nephropathy (DN). Heparan sulfate (HS) degradation induced by podocyte heparanase is the major cause of GBM thickening and abnormal perm-selectivity. In the present study, we aimed to e...
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| Format: | Article |
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Nature Portfolio
2017-07-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-017-06844-2 |
| _version_ | 1818751914688380928 |
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| author | Xiaofei An Lin Zhang Yanggang Yuan Bin Wang Qiuming Yao Ling Li Jisheng Zhang Ming He Jinan Zhang |
| author_facet | Xiaofei An Lin Zhang Yanggang Yuan Bin Wang Qiuming Yao Ling Li Jisheng Zhang Ming He Jinan Zhang |
| author_sort | Xiaofei An |
| collection | DOAJ |
| description | Abstract Glomerular basement membrane (GBM) damage plays a pivotal role in pathogenesis of albuminuria in diabetic nephropathy (DN). Heparan sulfate (HS) degradation induced by podocyte heparanase is the major cause of GBM thickening and abnormal perm-selectivity. In the present study, we aimed to examine the prophylactic effect of hyperoside on proteinuria development and GBM damage in DN mouse model and the cultured mouse podocytes. Pre-treatment with hyperoside (30 mg/kg/d) for four weeks could significantly decrease albuminuria, prevent GBM damage and oxidative stress in diabetes mellitus (DM) mice. Immunofluorescence staining, Real time PCR and Western blot analysis showed that decreased HS contents and increased heparanase expression in DN mice were also significantly improved by hyperoside pre-treatment. Meanwhile, transmission electron microscope imaging showed that hyperoside significantly alleviated GBM thickening in DN mice. In addition, hyperoside pre-treatment inhibited the increased heparanase gene (HPR1) promoter activity and heparanase expression induced by high glucose or reactive oxidative species (ROS) in cultured podocytes. Our data suggested that hyperoside has a prophylactic effect on proteinuria development and GBM damage in DM mice by decreasing podocyte heparanase expression. |
| first_indexed | 2024-12-18T04:43:08Z |
| format | Article |
| id | doaj.art-cb6d760cbd35466ebef99136a088e90b |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-18T04:43:08Z |
| publishDate | 2017-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-cb6d760cbd35466ebef99136a088e90b2022-12-21T21:20:40ZengNature PortfolioScientific Reports2045-23222017-07-017111210.1038/s41598-017-06844-2Hyperoside pre-treatment prevents glomerular basement membrane damage in diabetic nephropathy by inhibiting podocyte heparanase expressionXiaofei An0Lin Zhang1Yanggang Yuan2Bin Wang3Qiuming Yao4Ling Li5Jisheng Zhang6Ming He7Jinan Zhang8Department of Endocrinology, Jinshan Hospital of Fudan UniversityDepartment of Biochemistry and Molecular Cell Biology, Shanghai Jiao Tong University School of Medicine (SJTU-SM)Department of Nephrology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province People’s HospitalDepartment of Endocrinology, Jinshan Hospital of Fudan UniversityDepartment of Endocrinology, Jinshan Hospital of Fudan UniversityDepartment of Endocrinology, Jinshan Hospital of Fudan UniversityDepartment of Otorhinolaryngology, Affiliated Hospital of Qingdao UniversityDepartment of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine (SJTU-SM)Department of Endocrinology, Jinshan Hospital of Fudan UniversityAbstract Glomerular basement membrane (GBM) damage plays a pivotal role in pathogenesis of albuminuria in diabetic nephropathy (DN). Heparan sulfate (HS) degradation induced by podocyte heparanase is the major cause of GBM thickening and abnormal perm-selectivity. In the present study, we aimed to examine the prophylactic effect of hyperoside on proteinuria development and GBM damage in DN mouse model and the cultured mouse podocytes. Pre-treatment with hyperoside (30 mg/kg/d) for four weeks could significantly decrease albuminuria, prevent GBM damage and oxidative stress in diabetes mellitus (DM) mice. Immunofluorescence staining, Real time PCR and Western blot analysis showed that decreased HS contents and increased heparanase expression in DN mice were also significantly improved by hyperoside pre-treatment. Meanwhile, transmission electron microscope imaging showed that hyperoside significantly alleviated GBM thickening in DN mice. In addition, hyperoside pre-treatment inhibited the increased heparanase gene (HPR1) promoter activity and heparanase expression induced by high glucose or reactive oxidative species (ROS) in cultured podocytes. Our data suggested that hyperoside has a prophylactic effect on proteinuria development and GBM damage in DM mice by decreasing podocyte heparanase expression.https://doi.org/10.1038/s41598-017-06844-2 |
| spellingShingle | Xiaofei An Lin Zhang Yanggang Yuan Bin Wang Qiuming Yao Ling Li Jisheng Zhang Ming He Jinan Zhang Hyperoside pre-treatment prevents glomerular basement membrane damage in diabetic nephropathy by inhibiting podocyte heparanase expression Scientific Reports |
| title | Hyperoside pre-treatment prevents glomerular basement membrane damage in diabetic nephropathy by inhibiting podocyte heparanase expression |
| title_full | Hyperoside pre-treatment prevents glomerular basement membrane damage in diabetic nephropathy by inhibiting podocyte heparanase expression |
| title_fullStr | Hyperoside pre-treatment prevents glomerular basement membrane damage in diabetic nephropathy by inhibiting podocyte heparanase expression |
| title_full_unstemmed | Hyperoside pre-treatment prevents glomerular basement membrane damage in diabetic nephropathy by inhibiting podocyte heparanase expression |
| title_short | Hyperoside pre-treatment prevents glomerular basement membrane damage in diabetic nephropathy by inhibiting podocyte heparanase expression |
| title_sort | hyperoside pre treatment prevents glomerular basement membrane damage in diabetic nephropathy by inhibiting podocyte heparanase expression |
| url | https://doi.org/10.1038/s41598-017-06844-2 |
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