Interference of the cold shock protein YB-1 and progranulin on tumor necrosis factor-alpha signalling in inflammatory renal disease

冷休克蛋白 YB-1 和颗粒体蛋白前体对炎症性肾病肿瘤坏死因子-α 信号传导的干扰

• 批准号: 276732887
• 负责人: Privatdozent Dr. Jonathan Lindquist, Ph.D.
• 金额: --
• 依托单位: Bereich Nephrologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2015
• 资助国家: 德国
• 起止时间: 2014-12-31 至 2018-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/276732887?language=en
• 关键词: Interference; cold; shock; protein; YB

Y-box binding protein-1 (YB-1) belongs to the human cold shock protein superfamily. Its known functions relate to gene transcription and RNA translation that permit cell phenotypic changes and cell-cell communication. Evidence links YB-1 expression with cytokine synthesis in inflammatory kidney disease. Our data demonstrate a pronounced mesangial cell expression of YB-1 and even active protein secretion in models of mesangioproliferative disease, as well as an interaction of YB 1 with the anti-inflammatory protein progranulin. The current proposal aims to investigate the functional role(s) of the YB-1:progranulin interaction in inflammatory kidney disease. First we will address how YB-1 influences the anti-inflammatory activity of progranulin. Next we shall investigate whether the loss of YB-1 or progranulin alters the onset or progression of inflammatory kidney disease. Additionally, we shall test whether manipulating YB-1 levels alter the course of inflammatory kidney disease. And finally, we shall determine whether progranulin and tumor necrosis factor alpha levels are suitable markers for inflammatory kidney disease activity. The proposal addresses pivotal questions on the functional role(s) of YB-1 and progranulin in the pathogenesis of inflammatory kidney diseases and may open new avenues to diagnostic and therapeutic strategies.

Y-box binding protein-1 （YB-1）属于人冷休克蛋白超家族。其已知功能与基因转录和RNA翻译有关，这些功能允许细胞表型改变和细胞间通信。证据表明炎症性肾病中YB-1表达与细胞因子合成有关。我们的数据表明，在系膜血管增生性疾病模型中，系膜细胞明显表达YB-1，甚至活性蛋白分泌，以及YB-1与抗炎蛋白前颗粒蛋白的相互作用。目前的提案旨在研究YB-1：前颗粒蛋白相互作用在炎症性肾脏疾病中的功能作用。首先，我们将讨论YB-1如何影响颗粒蛋白前的抗炎活性。接下来，我们将研究YB-1或颗粒前蛋白的缺失是否会改变炎症性肾病的发生或进展。此外，我们将测试控制YB-1水平是否会改变炎症性肾病的病程。最后，我们将确定颗粒前蛋白和肿瘤坏死因子α水平是否适合作为炎症性肾脏疾病活动性的标志物。该建议解决了关于YB-1和前颗粒蛋白在炎症性肾脏疾病发病机制中的功能作用的关键问题，并可能为诊断和治疗策略开辟新的途径。

项目成果

Cold Shock Proteins Mediate GN with Mesangioproliferation.

• DOI: 10.1681/asn.2015121367
• 发表时间: 2016-05
• 期刊: Journal of the American Society of Nephrology : JASN
• 作者: Cheng Zhu;E. Sauter;A. Schreiter;Claudia R C van Roeyen;T. Ostendorf;J. Floege;F. Gembardt;C. Hugo;B. Isermann;J. Lindquist;P. Mertens

Differential distribution of Y-box-binding protein 1 and cold shock domain protein A in developing and adult human brain

• DOI: 10.1007/s00429-014-0786-9
• 发表时间: 2015-07-01
• 期刊: BRAIN STRUCTURE & FUNCTION
• 影响因子: 3.1
• 作者: Bernstein, Hans-Gert;Lindquist, Jonathan A.;Mertens, Peter R.
• 通讯作者: Mertens, Peter R.