Phenotypic change of mesangial cells in the glomerulosclerosis

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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