Phenotypic change of mesangial cells in the glomerulosclerosis

肾小球硬化症中系膜细胞的表型变化

• 批准号: 05670955
• 负责人: KASHIHARA Naoki
• 金额: $ 1.22万
• 依托单位: Okayama University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05670955/
• 关键词: phenotypic change; Glomerulonephritis; mesangial cell; 糸球体硬化; ミオシン; 細胞骨格蛋白; 形質変化

Glomerulosclerosis is characterized by progressive ECM accumulation and glomerular cell loss. The mechanism of ECM accumulation has been well explored in recent years. In contrast, the mechanism of cell death in the process of glomerulosclerosis is poorly understood. We first found that apoptosis is involved in the glomerular cell deletion of progressive glomerulosclerosis. Then we also found phenotype of mesangial cell alters in the process of glomerular injuries. It is well known that cell-phenotype, such as proliferation and differentiation, are greatly influenced by the extracellular matrix (ECM) surrounding the cells. In diseased conditions, the mesangial matrix is altered both quantitatively and qualitatively. The increased ECM includes not only normal components but also de novo induction of type I and III collagens, which are not normally expressed in the glomerulus. Several studies suggested that the alteration of the composition of the ECM affected the behavior of the mesangi … More al cells including proliferation, migration and differentiation. Several studies revealed that cell attachment to ECM is required for suppression of apoptosis. It is therefore of interest to determine whether cell-matrix interactions may influence apoptosis of the mesangial cells. We hypothesized that normal ECM may support the survival of mesangial cell and prevent their death. Alteration in ECM constituents may lessen the survival signals to mesangial cell and increase their susceptibility to stimuli that induce apoptosis. Firstly, we investigated the difference in the susceptibility to apoptotic stimuli of the mesangial cells cultured on various ECM components. Accumulation of ECM and progressive cell loss are the must prominent features of glomerulosclerosis. ECM components are altered both quantitatively and qualitatively in the process leading to sclerosis. Altered phenotype may influence the susceptibility to apoptotic stimuli of mesangial cells, such as ROS. In such situation, glomerular cells are easily lost by apoptosis. The mechanism of glomerular cell apoptosis requires further study to gain new insights into the treatment of renal diseases and prevention of subsequent glomerular scarring. Less

肾小球硬化的特征在于进行性ECM积聚和肾小球细胞损失。近年来，ECM积累的机制已被很好地探索。相反，肾小球硬化过程中细胞死亡的机制知之甚少。我们首次发现细胞凋亡参与了进行性肾小球硬化的肾小球细胞缺失。同时发现肾小球损伤过程中系膜细胞表型发生改变。众所周知，细胞表型，如增殖和分化，受到细胞周围细胞外基质（ECM）的极大影响。在疾病状态下，系膜基质在数量和质量上都发生了变化。增加的ECM不仅包括正常组分，而且包括I型和III型胶原的从头诱导，其通常不在肾小球中表达。一些研究表明，ECM成分的改变影响了系膜的行为 ...更多信息 al细胞的增殖、迁移和分化。几项研究表明，细胞附着到ECM是抑制细胞凋亡所必需的。因此，确定细胞-基质相互作用是否可能影响系膜细胞的凋亡是有意义的。我们推测正常的ECM可能支持肾小球系膜细胞的存活并阻止其死亡。细胞外基质成分的改变可能减少了对系膜细胞的存活信号，并增加了它们对诱导凋亡的刺激的敏感性。首先，我们研究了不同ECM成分培养的系膜细胞对凋亡刺激敏感性的差异。肾小球硬化的主要特征是细胞外基质（ECM）的积聚和细胞的进行性丢失。ECM成分在导致硬化的过程中在数量和质量上都发生了变化。表型改变可能影响系膜细胞对ROS等凋亡刺激的敏感性。在这种情况下，肾小球细胞容易因凋亡而丢失。肾小球细胞凋亡的机制需要进一步研究，以获得新的见解，为肾脏疾病的治疗和预防随后的肾小球瘢痕。少

项目成果

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Makino H、Kashihara N、Sugiyama H、Kanao K 等人：“糖尿病肾病中系膜的表型变化。”J 糖尿病及其并发症。

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Makino H, Kashihara N, Sugiyama H, Kanao K, et al.: "Phenotypic modulation of the mesangium reflected by contractile proteins in diabetes."Diabetes. 45. 488-495 (1996)

Makino H、Kashihara N、Sugiyama H、Kanao K 等人：“糖尿病中收缩蛋白反映的系膜表型调节。”糖尿病。