High glucose induces platelet derived growth factor-C via carbohydrate response element binding protein in glomeruｌar mesangial cells

• Material Type: 博士論文
• Title: High glucose induces platelet derived growth factor-C via carbohydrate response element binding protein in glomeruｌar mesangial cells
• Volume: 4 6
• Author/Editor: 橘内, 博哉
• Publication Date: 2016-05
• Publication Date (W3CDTF): 2016-05
• Periodical title: Physiological Reports
• Degree grantor/type: 旭川医科大学
• Date Granted: 2014-03-25
• Date Granted (W3CDTF): 2014-03-25
• Dissertation Number: 甲第456号
• Degree Type: 博士（医学）
• Conferring No. (Dissertation): 甲第456号
• Text Language Code: eng
• Subject Heading: Carbohydrate response element‐binding protein; diabetic nephropathy; mesangial cells; platelet‐derived growth factor‐C; transcription facto
• Note (General): Persistent high concentration of glucose causes cellular stress and damage in diabetes via derangement of gene expressions. We previously reported high glucose activates hypoxia-inducible factor-1αand downstream gene expression in mesangial cells, leading to an extracellular matrix expansion in the glomeruli. A glucose-responsive transcription factor carbohydrate response element-binding protein (ChREBP) is a key mediator for such perturbation of gene regulation. To provide insight into glucose-mediated gene regulation in mesangial cells, we performed chromatin immunoprecipitation followed byDNAmicroarray analysis and identified platelet-derived growth factor-C (PDGF-C) as a novel target gene of ChREBP In streptozotocin-induced diabetic mice, glomerular cells showed a significant increase inPDGF-C expression; the ratio ofPDGF-C-positive cells to the total number glomerular cells demonstrated more than threefold increase when compared with control animals. In cultured human mesangial cells, high glucose enhanced expression ofPDGF-C protein by 1.9-fold. Knock-down of ChREBPabrogated this induction response. UpregulatedPDGF-C contributed to the production of typeIVand typeVIcollagen, possibly via an autocrine mechanism. Interestingly, urinaryPDGF-C levels in diabetic model mice were significantly elevated in a fashion similar to urinary albumin. Taken together, we hypothesize that a high glucose-mediated induction ofPDGF-C via ChREBPin mesangial cells contributes to the development of glomerular mesangial expansion in diabetes, which may provide a platform for novel predictive and therapeutic strategies for diabetic nephropathy.; identifier:PMID:27033449
• DOI: info:doi/10.14814/phy2.12730; https://doi.org/info:doi/10.14814/phy2.12730
• Persistent ID (NDL): info:ndljp/pid/10200465; https://dl.ndl.go.jp/pid/10200465
• Collection: 障害者向け資料
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• Collection (particular): 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文; https://dl.ndl.go.jp/collections/A00014
• Acquisition Basis: 博士論文（自動収集）
• Date Accepted (W3CDTF): 2016-10-01T18:16:16+09:00
• Format (IMT): application/pdf
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• Periodical Title (URI): http://amcor.asahikawa-med.ac.jp/modules/xoonips/detail.php?id=20140325_K456
• Data Provider (Database): 国立国会図書館 : 国立国会図書館デジタルコレクション; https://dl.ndl.go.jp