GdCl3 attenuates the glomerular sclerosis of streptozotocin (STZ) induced diabetic rats via inhibiting TGF-β/Smads signal pathway
Diabetic nephropathy (DN) is the most serious end-stage renal disease which characterized by renal glomerular sclerosis including glomerular hypertrophy, glomerular basement membrane (GBM) thickening, mesangial expansion and renal fibrosis. TGF-β/Smads signal pathway plays a crucial role in the deve...
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| Format: | Article |
| Language: | English |
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Elsevier
2020-02-01
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| Series: | Journal of Pharmacological Sciences |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1347861319341738 |
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| author | Jialin Li Bing Wu Haibo Hu Xiansong Fang Zhiping Liu Suzhen Wu |
| author_facet | Jialin Li Bing Wu Haibo Hu Xiansong Fang Zhiping Liu Suzhen Wu |
| author_sort | Jialin Li |
| collection | DOAJ |
| description | Diabetic nephropathy (DN) is the most serious end-stage renal disease which characterized by renal glomerular sclerosis including glomerular hypertrophy, glomerular basement membrane (GBM) thickening, mesangial expansion and renal fibrosis. TGF-β/Smads signal pathway plays a crucial role in the development of renal fibrosis. In this study, we found that GdCl3 which was an agonist of Calcium-sensing receptor (CaSR) could repress the activation of TGF-β/Smads signal pathway induced by TGF-β1 or high glucose and then alleviated the accumulation of extracellular matrix (ECM) in mesangial cells and the kidney of type1 diabetic rats. Further study indicated that GdCl3 could induce the binding of CaSR and TβR II and then both of these two receptors translocated from cell membrane to cytoplasm, in this case, TβR II on the cell membrane was decreased and then desensitized to the stimulation of its ligand TGF-β1, so that the activation of its downstream factors such as Smad2 and Smad3 were blocked, finally, ECM expression in mesangial cells were inhibited. We concluded that GdCl3 could alleviate the accumulation of ECM in mesangial cells via antagonizing TGF-β/Smads signal pathway in diabetes mellitus. Keywords: GdCl3, TGF-β/Smads signal pathway, Diabetic nephropathy, Extracellular matrix, Calcium-sensing receptor |
| first_indexed | 2024-12-10T14:47:27Z |
| format | Article |
| id | doaj.art-cf771280a7a441e0a0fb7d43d93e4f20 |
| institution | Directory Open Access Journal |
| issn | 1347-8613 |
| language | English |
| last_indexed | 2024-12-10T14:47:27Z |
| publishDate | 2020-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Pharmacological Sciences |
| spelling | doaj.art-cf771280a7a441e0a0fb7d43d93e4f202022-12-22T01:44:32ZengElsevierJournal of Pharmacological Sciences1347-86132020-02-0114224149GdCl3 attenuates the glomerular sclerosis of streptozotocin (STZ) induced diabetic rats via inhibiting TGF-β/Smads signal pathwayJialin Li0Bing Wu1Haibo Hu2Xiansong Fang3Zhiping Liu4Suzhen Wu5College of Pharmacy, Gannan Medical University, Ganzhou 341000, Jiangxi Province, ChinaSchool of Basic Medicine, Gannan Medical University, Ganzhou 341000, Jiangxi Province, ChinaCollege of Pharmacy, Gannan Medical University, Ganzhou 341000, Jiangxi Province, ChinaThe First Affiliated Hospital, Gannan Medical University, Ganzhou 341000, Jiangxi Province, ChinaSchool of Basic Medicine, Gannan Medical University, Ganzhou 341000, Jiangxi Province, China; Corresponding author.School of Basic Medicine, Gannan Medical University, Ganzhou 341000, Jiangxi Province, China; Corresponding author. School of Basic Medicine, Gannan Medical University, 1 Yixueyuan Road, Ganzhou 341000, Jiangxi Province, China.Diabetic nephropathy (DN) is the most serious end-stage renal disease which characterized by renal glomerular sclerosis including glomerular hypertrophy, glomerular basement membrane (GBM) thickening, mesangial expansion and renal fibrosis. TGF-β/Smads signal pathway plays a crucial role in the development of renal fibrosis. In this study, we found that GdCl3 which was an agonist of Calcium-sensing receptor (CaSR) could repress the activation of TGF-β/Smads signal pathway induced by TGF-β1 or high glucose and then alleviated the accumulation of extracellular matrix (ECM) in mesangial cells and the kidney of type1 diabetic rats. Further study indicated that GdCl3 could induce the binding of CaSR and TβR II and then both of these two receptors translocated from cell membrane to cytoplasm, in this case, TβR II on the cell membrane was decreased and then desensitized to the stimulation of its ligand TGF-β1, so that the activation of its downstream factors such as Smad2 and Smad3 were blocked, finally, ECM expression in mesangial cells were inhibited. We concluded that GdCl3 could alleviate the accumulation of ECM in mesangial cells via antagonizing TGF-β/Smads signal pathway in diabetes mellitus. Keywords: GdCl3, TGF-β/Smads signal pathway, Diabetic nephropathy, Extracellular matrix, Calcium-sensing receptorhttp://www.sciencedirect.com/science/article/pii/S1347861319341738 |
| spellingShingle | Jialin Li Bing Wu Haibo Hu Xiansong Fang Zhiping Liu Suzhen Wu GdCl3 attenuates the glomerular sclerosis of streptozotocin (STZ) induced diabetic rats via inhibiting TGF-β/Smads signal pathway Journal of Pharmacological Sciences |
| title | GdCl3 attenuates the glomerular sclerosis of streptozotocin (STZ) induced diabetic rats via inhibiting TGF-β/Smads signal pathway |
| title_full | GdCl3 attenuates the glomerular sclerosis of streptozotocin (STZ) induced diabetic rats via inhibiting TGF-β/Smads signal pathway |
| title_fullStr | GdCl3 attenuates the glomerular sclerosis of streptozotocin (STZ) induced diabetic rats via inhibiting TGF-β/Smads signal pathway |
| title_full_unstemmed | GdCl3 attenuates the glomerular sclerosis of streptozotocin (STZ) induced diabetic rats via inhibiting TGF-β/Smads signal pathway |
| title_short | GdCl3 attenuates the glomerular sclerosis of streptozotocin (STZ) induced diabetic rats via inhibiting TGF-β/Smads signal pathway |
| title_sort | gdcl3 attenuates the glomerular sclerosis of streptozotocin stz induced diabetic rats via inhibiting tgf β smads signal pathway |
| url | http://www.sciencedirect.com/science/article/pii/S1347861319341738 |
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