دورية أكاديمية
Transcription Factor Egr1 is Involved in High Glucose-Induced Proliferation and Fibrosis in Rat Glomerular Mesangial Cells
| العنوان: | Transcription Factor Egr1 is Involved in High Glucose-Induced Proliferation and Fibrosis in Rat Glomerular Mesangial Cells |
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| المؤلفون: | Dan Wang, Mei-Ping Guan, Zong-Ji Zheng, Wen-Qi Li, Fu-Ping Lyv, Ruo-Yu Pang, Yao-Ming Xue |
| المصدر: | Cellular Physiology and Biochemistry, Vol 36, Iss 6, Pp 2093-2107 (2015) |
| بيانات النشر: | Cell Physiol Biochem Press GmbH & Co KG, 2015. |
| سنة النشر: | 2015 |
| المجموعة: | LCC:Physiology LCC:Biochemistry |
| مصطلحات موضوعية: | Egr1, Diabetic nephropathy, TGF-β1, Mesangial cells, Extracellular matrix, Physiology, QP1-981, Biochemistry, QD415-436 |
| الوصف: | 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. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1015-8987 1421-9778 |
| Relation: | http://www.karger.com/Article/FullText/430177; https://doaj.org/toc/1015-8987; https://doaj.org/toc/1421-9778 |
| DOI: | 10.1159/000430177 |
| URL الوصول: | https://doaj.org/article/9b5a7c7179ff455baf3bcec2462a2453 |
| رقم الأكسشن: | edsdoj.9b5a7c7179ff455baf3bcec2462a2453 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 10158987 14219778 |
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| DOI: | 10.1159/000430177 |