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 µM 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.
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May 23 2001
Bimodal effects of platelet-derived growth factor on rat mesangial cell proliferation and death, and the role of lysophosphatidic acid in cell survival
Chiyoko N. INOUE;
Chiyoko N. INOUE
*Department of Pediatrics, Tohoku University School of Medicine, Sendai, Japan
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Isao NAGANO;
Isao NAGANO
†Department of Neurology, Tohoku University School of Medicine, Sendai, Japan
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Ryo ICHINOHASAMA;
Ryo ICHINOHASAMA
‡Department of Oral Pathology, Tohoku University School of Dentistry, Sendai, Japan
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Natsumi ASATO;
Natsumi ASATO
§Biomedical Laboratory-Pathology and Cytology Center, Saitama, Japan
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Yoshiaki KONDO;
Yoshiaki KONDO
*Department of Pediatrics, Tohoku University School of Medicine, Sendai, Japan
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Kazuie IINUMA
Kazuie IINUMA
*Department of Pediatrics, Tohoku University School of Medicine, Sendai, Japan
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Publisher: Portland Press Ltd
Received:
November 02 2000
Revision Received:
January 30 2001
Accepted:
March 21 2001
Online ISSN: 1470-8736
Print ISSN: 0143-5221
The Biochemical Society and the Medical Research Society © 2001
2001
Clin Sci (Lond) (2001) 101 (1): 11–19.
Article history
Received:
November 02 2000
Revision Received:
January 30 2001
Accepted:
March 21 2001
Citation
Chiyoko N. INOUE, Isao NAGANO, Ryo ICHINOHASAMA, Natsumi ASATO, Yoshiaki KONDO, Kazuie IINUMA; Bimodal effects of platelet-derived growth factor on rat mesangial cell proliferation and death, and the role of lysophosphatidic acid in cell survival. Clin Sci (Lond) 1 July 2001; 101 (1): 11–19. doi: https://doi.org/10.1042/cs1010011
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