MESANGIAL CELL APOPTOSIS - THE MAJOR MECHANISM FOR RESOLUTION OF GLOMERULAR HYPERCELLULARITY IN EXPERIMENTAL MESANGIAL PROLIFERATIVE NEPHRITIS
MESANGIAL CELL APOPTOSIS - THE MAJOR MECHANISM FOR RESOLUTION OF GLOMERULAR HYPERCELLULARITY IN EXPERIMENTAL MESANGIAL PROLIFERATIVE NEPHRITIS
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DOI：
10.1172/jci117565
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发表时间：
1994-11-01
影响因子：
15.9
通讯作者：
SAVILL, J
中科院分区：
文献类型：
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作者：
BAKER, AJ;MOONEY, A;SAVILL, J
系膜细胞数量的增加可能预示着肾小球疤痕形成，但它们并不是不可逆转的。这项研究寻找清除多余肾小球系膜细胞的机制。一小部分培养的系膜细胞表现出典型的细胞凋亡（程序性细胞死亡）的形态学特征，这种特征会因生长因子剥夺或暴露于放线菌酮而增加，已知这些刺激会增加其他细胞类型的细胞凋亡。通过典型的核小体间染色质裂解证实细胞凋亡。在体内，Thy1.1抗体诱导大鼠自限性系膜增殖中获得了系膜细胞凋亡导致邻近系膜细胞吞噬的清晰形态学证据，细胞凋亡发生频率比健康大鼠肾小球高10倍。事实上，Thy1.1肾炎中肾小球细胞数量的变化强烈表明细胞凋亡是平衡细胞分裂的主要细胞清除机制，从而介导实验性系膜增殖中肾小球细胞过多的解决。
Increases in mesangial cell number may herald glomerular scarring, but they are not irreversible. This study sought mechanisms by which surplus glomerular mesangial cells can be cleared. A small proportion of cultured mesangial cells exhibited typical morphological features of apoptosis (programmed cell death), which was increased by growth factor deprivation or exposure to cycloheximide, stimuli known to increase apoptosis in other cell types. Apoptosis was confirmed by typical internucleosomal chromatin cleavage. In vivo, clear morphological evidence of mesangial apoptosis leading to phagocytosis by neighboring mesangial cells was obtained in self-limited mesangial proliferation induced in rats by Thy1.1 antibody, apoptosis occurring similar to 10-fold more frequently than in the healthy rat glomerulus. Indeed, changes in glomerular cell number in Thy1.1 nephritis strongly suggested that apoptosis is the major cell clearance mechanism counterbalancing cell division, thereby mediating resolution of glomerular hypercellularity in experimental mesangial proliferation.