Inoue C N, Nagano I, Ichinohasama R, Asato N, Kondo Y, Iinuma K
Department of Pediatrics, Tohoku University School of Medicine, Sendai, Japan.
Clin Sci (Lond). 2001 Jul;101(1):11-9.
Although mesangial cell death has been shown to be correlated with mesangial cell mitosis in vivo, little is known about how these two apparently opposite events are regulated. We show that the addition of platelet-derived growth factor (PDGF; 10-50 ng/ml) to primary cultured rat mesangial cells for 24 h caused continuous proliferation along with simultaneous cell death. This process was accompanied by the fragmentation of DNA into nucleosomal oligomers, the development of apoptotic morphological changes in the nucleus, and increased expression of p53. Accumulation of lactate dehydrogenase (LDH) was also observed in the culture medium, suggesting that both apoptosis and necrosis are involved in the cell death mechanisms observed. We also observed that addition of 30 microM lysophosphatidic acid (LPA) to the culture medium greatly suppressed PDGF-induced cell death, leading to synergistically enhanced mesangial cell proliferation. DNA fragmentation, p53 expression and LDH release were all suppressed by LPA. We suggest that PDGF is a bifunctional molecule in mesangial cells that evokes both cell proliferation and cell death simultaneously, whereas LPA is a survival factor. We speculate that PDGF and LPA may play important roles in the progression or exacerbation of proliferative glomerulonephritis.
尽管在体内已表明系膜细胞死亡与系膜细胞有丝分裂相关，但对于这两个明显相反的事件是如何被调控的却知之甚少。我们发现，向原代培养的大鼠系膜细胞中添加血小板衍生生长因子（PDGF；10 - 50 ng/ml）24小时，会导致细胞持续增殖并同时发生细胞死亡。这个过程伴随着DNA断裂成核小体寡聚体、细胞核出现凋亡形态学变化以及p53表达增加。在培养基中还观察到乳酸脱氢酶（LDH）的积累，这表明凋亡和坏死都参与了所观察到的细胞死亡机制。我们还观察到，向培养基中添加30微摩尔溶血磷脂酸（LPA）可极大地抑制PDGF诱导的细胞死亡，从而协同增强系膜细胞增殖。LPA抑制了DNA片段化、p53表达和LDH释放。我们认为，PDGF在系膜细胞中是一种双功能分子，可同时引发细胞增殖和细胞死亡，而LPA是一种存活因子。我们推测，PDGF和LPA可能在增殖性肾小球肾炎的进展或恶化中起重要作用。
