Phenotypic change of mesangial cells in the glomerulosclerosis

肾小球硬化以进行性ECM积累和肾小球细胞损失为特征。近年来，ECM的积累机制得到了很好的探讨。相比之下，肾小球硬化过程中细胞死亡的机制尚不清楚。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。我们还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，很大程度上受到细胞周围细胞外基质（ECM）的影响。在病变情况下，系膜基质在数量和质量上都发生改变。增加的ECM不仅包括正常成分，还包括在肾小球中不正常表达的I型和III型胶原的新生诱导。一些研究表明，ECM成分的改变影响了系膜细胞的行为，包括增殖、迁移和分化。一些研究表明，细胞附着于ECM是抑制细胞凋亡所必需的。因此，确定细胞-基质相互作用是否会影响系膜细胞的凋亡是很有意义的。我们推测正常的外基质可能支持系膜细胞的存活并阻止其死亡。ECM成分的改变可能会减少传递给系膜细胞的存活信号，增加其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。ECM积累和进行性细胞丢失是肾小球硬化的最显著特征。在导致硬化的过程中，ECM成分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（如ROS）对凋亡刺激的敏感性。在这种情况下，肾小球细胞很容易因凋亡而丢失。肾小球细胞凋亡的机制有待进一步研究，为肾脏疾病的治疗和后续肾小球瘢痕形成的预防提供新的见解。少

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