Tissue specific transcriptional regulation of mesangium-predominant gene, megsin

系膜优势基因 megsin 的组织特异性转录调控

• 批准号: 11671053
• 负责人: INAGI Reiko
• 金额: $ 2.3万
• 依托单位: Tokai University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11671053/
• 关键词: megsin; transcriptional factor; mesangial cells; mesangioproliferative glomerulonephritis; promoter; serpin; 進行性糸球体障害; メサンギウム細胞特異的転写調節機構; 特異的DNA結合蛋白

We have recently cloned cDNA of a new human mesangium-predominant gene, megsin, which is a novel member of the serpin superfamily. The purpose of this study was to investigate the mechanisms of mesangial cell-dependent expression of this gene. The megsin gene was localized in chromosome 18q21.3, close to the other serpin genes. The gene spanned 20 kbp, and the genomic structure of the serpin superfamily was highly conserved. The sequence analysis demonstrated a consensus promoter segment within the 5^1-flanking region. Reporter assays in various cell types demonstrated strong promoter activity of this region in mesangial cells. We identified two positive regulatory elements, utilizing deletion mutagenesis and site-directed mutagenesis analysis. Electrophoretic mobility shift assays showed two unidentified transcription factors that bind to the -129 to -88 region. These transcription factors were predominantly expressed in mesangial cells. In Conclusion, high levels of megsin in mesangial cells could be explained by dominant expression of the transcription factors. Detection of the important cis-elements in the promoter and demonstration of these transcription factors in mesangial cells encourage us to perform further studies of this gene for understanding of mesangium-predominant gene expression.

我们最近克隆了一个新的人类系膜优势基因，megsin，这是一个新的丝氨酸蛋白酶抑制剂超家族成员的cDNA。本研究的目的是探讨该基因表达依赖于系膜细胞的机制。megsin基因定位于染色体18q21.3，与其他丝氨酸蛋白酶抑制剂基因位置相近。该基因全长约20 kbp，基因组结构高度保守。序列分析表明在5^1-侧翼区域内存在共有启动子片段。在各种类型的细胞中的报告基因检测表明，该区域在系膜细胞中具有很强的启动子活性。我们确定了两个积极的调控元件，利用缺失突变和定点突变分析。电泳迁移率变动分析表明，两个身份不明的转录因子，结合到-129至-88区域。这些转录因子主要在系膜细胞中表达。结论：系膜细胞中megsin的高表达可能与转录因子的优势表达有关。启动子中重要顺式元件的检测以及系膜细胞中这些转录因子的证实鼓励我们对该基因进行进一步研究，以了解系膜主导基因的表达。

项目成果

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Miyata T et. al: "Mechanism of inhibitory effect of 2-isopropylidenehydrazono-4-oxo-thiazolidin-5ylacetanilide (OPB-9195) on AGE and ALE formation"J Am Soc Nephrol. (in press).

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