Transcription Factor Egr1 is Involved in High Glucose-Induced Proliferation and Fibrosis in Rat Glomerular Mesangial Cells
Backgroud: Diabetic nephropathy is one of the most frequent causes of end-stage renal disease and is associated with proliferation of glomerular mesangial cells (MCs) and excessive production of the extracellular matrix (ECM). Several studies have shown that early growth response factor 1 (Egr1) pla...
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| Format: | Article |
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Cell Physiol Biochem Press GmbH & Co KG
2015-07-01
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| Series: | Cellular Physiology and Biochemistry |
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| Online Access: | http://www.karger.com/Article/FullText/430177 |
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| author | Dan Wang Mei-Ping Guan Zong-Ji Zheng Wen-Qi Li Fu-Ping Lyv Ruo-Yu Pang Yao-Ming Xue |
| author_facet | Dan Wang Mei-Ping Guan Zong-Ji Zheng Wen-Qi Li Fu-Ping Lyv Ruo-Yu Pang Yao-Ming Xue |
| author_sort | Dan Wang |
| collection | DOAJ |
| description | Backgroud: Diabetic nephropathy is one of the most frequent causes of end-stage renal disease and is associated with proliferation of glomerular mesangial cells (MCs) and excessive production of the extracellular matrix (ECM). Several studies have shown that early growth response factor 1 (Egr1) plays a key role in renal fibrosis by regulating the expression of genes encoding ECM components. However, whether Egr1 also contributes to diabetic nephropathy is unclear. Methods: In the present study, we compared the expression of Egr1 in kidneys from OLETF rats with spontaneous type 2 diabetes and healthy LETO rats. We also examined whether high glucose and TGF-β1 signaling up-regulated Egr1 expression in cultured MCs, and whether Egr1 expression influenced MC proliferation and expression of ECM genes. Results: We found that higher expression of Egr1 and TGF-β1, at both the mRNA and protein levels, the kidneys from OLETF rats vs. LETO rats. High glucose or TGF-β1 signaling rapidly up-regulated expression of Egr1 mRNA and protein in cultured MCs. Overexpressing Egr1 in MCs by transfection with M61-Egr1 plasmid or treatment with high glucose up-regulated expression of fibronectin, type IV collagen and TGF-β1, and promoted MC proliferation. Conversely, siRNA-mediated silencing of Egr1 expression down-regulated these genes and inhibited MC proliferation. Chromatin immunoprecipitation (ChIP) assays revealed that Egr1 bound to the TGF-β1 promoter. Conclusion: Our results provide strong evidence that Egr1 contributes to diabetic nephropathy by enhancing MC proliferation and ECM production, in part by interacting with TGF-β1. |
| first_indexed | 2024-12-10T12:05:53Z |
| format | Article |
| id | doaj.art-9b5a7c7179ff455baf3bcec2462a2453 |
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| issn | 1015-8987 1421-9778 |
| language | English |
| last_indexed | 2024-12-10T12:05:53Z |
| publishDate | 2015-07-01 |
| publisher | Cell Physiol Biochem Press GmbH & Co KG |
| record_format | Article |
| series | Cellular Physiology and Biochemistry |
| spelling | doaj.art-9b5a7c7179ff455baf3bcec2462a24532022-12-22T01:49:28ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782015-07-013662093210710.1159/000430177430177Transcription Factor Egr1 is Involved in High Glucose-Induced Proliferation and Fibrosis in Rat Glomerular Mesangial CellsDan WangMei-Ping GuanZong-Ji ZhengWen-Qi LiFu-Ping LyvRuo-Yu PangYao-Ming XueBackgroud: Diabetic nephropathy is one of the most frequent causes of end-stage renal disease and is associated with proliferation of glomerular mesangial cells (MCs) and excessive production of the extracellular matrix (ECM). Several studies have shown that early growth response factor 1 (Egr1) plays a key role in renal fibrosis by regulating the expression of genes encoding ECM components. However, whether Egr1 also contributes to diabetic nephropathy is unclear. Methods: In the present study, we compared the expression of Egr1 in kidneys from OLETF rats with spontaneous type 2 diabetes and healthy LETO rats. We also examined whether high glucose and TGF-β1 signaling up-regulated Egr1 expression in cultured MCs, and whether Egr1 expression influenced MC proliferation and expression of ECM genes. Results: We found that higher expression of Egr1 and TGF-β1, at both the mRNA and protein levels, the kidneys from OLETF rats vs. LETO rats. High glucose or TGF-β1 signaling rapidly up-regulated expression of Egr1 mRNA and protein in cultured MCs. Overexpressing Egr1 in MCs by transfection with M61-Egr1 plasmid or treatment with high glucose up-regulated expression of fibronectin, type IV collagen and TGF-β1, and promoted MC proliferation. Conversely, siRNA-mediated silencing of Egr1 expression down-regulated these genes and inhibited MC proliferation. Chromatin immunoprecipitation (ChIP) assays revealed that Egr1 bound to the TGF-β1 promoter. Conclusion: Our results provide strong evidence that Egr1 contributes to diabetic nephropathy by enhancing MC proliferation and ECM production, in part by interacting with TGF-β1.http://www.karger.com/Article/FullText/430177Egr1Diabetic nephropathyTGF-β1Mesangial cellsExtracellular matrix |
| spellingShingle | Dan Wang Mei-Ping Guan Zong-Ji Zheng Wen-Qi Li Fu-Ping Lyv Ruo-Yu Pang Yao-Ming Xue Transcription Factor Egr1 is Involved in High Glucose-Induced Proliferation and Fibrosis in Rat Glomerular Mesangial Cells Cellular Physiology and Biochemistry Egr1 Diabetic nephropathy TGF-β1 Mesangial cells Extracellular matrix |
| title | Transcription Factor Egr1 is Involved in High Glucose-Induced Proliferation and Fibrosis in Rat Glomerular Mesangial Cells |
| title_full | Transcription Factor Egr1 is Involved in High Glucose-Induced Proliferation and Fibrosis in Rat Glomerular Mesangial Cells |
| title_fullStr | Transcription Factor Egr1 is Involved in High Glucose-Induced Proliferation and Fibrosis in Rat Glomerular Mesangial Cells |
| title_full_unstemmed | Transcription Factor Egr1 is Involved in High Glucose-Induced Proliferation and Fibrosis in Rat Glomerular Mesangial Cells |
| title_short | Transcription Factor Egr1 is Involved in High Glucose-Induced Proliferation and Fibrosis in Rat Glomerular Mesangial Cells |
| title_sort | transcription factor egr1 is involved in high glucose induced proliferation and fibrosis in rat glomerular mesangial cells |
| topic | Egr1 Diabetic nephropathy TGF-β1 Mesangial cells Extracellular matrix |
| url | http://www.karger.com/Article/FullText/430177 |
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