Bimodal effects of platelet-derived growth factor on rat mesangial cell proliferation and death, and the role of lysophosphatidic acid in cell survival

2001 ◽  
Vol 101 (1) ◽  
pp. 11 ◽  
Author(s):  
Chiyoko N. INOUE ◽  
Isao NAGANO ◽  
Ryo ICHINOHASAMA ◽  
Natsumi ASATO ◽  
Yoshiaki KONDO ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Growth Factor ◽  
Cell Survival ◽  
Lysophosphatidic Acid ◽  
Mesangial Cell ◽  
Platelet Derived Growth Factor ◽  
Mesangial Cell Proliferation

Bimodal effects of platelet-derived growth factor on rat mesangial cell proliferation and death, and the role of lysophosphatidic acid in cell survival

2001 ◽  
Vol 101 (1) ◽  
pp. 11-19 ◽  
Author(s):  
Chiyoko N. INOUE ◽  
Isao NAGANO ◽  
Ryo ICHINOHASAMA ◽  
Natsumi ASATO ◽  
Yoshiaki KONDO ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Death ◽  
Growth Factor ◽  
Lysophosphatidic Acid ◽  
Culture Medium ◽  
Mesangial Cell ◽  
Mesangial Cells ◽  
Platelet Derived Growth Factor ◽  
P53 Expression ◽  
Mesangial Cell Proliferation

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.

scholarly journals Role of platelet-derived growth factor in glomerular disease.

1993 ◽  
Vol 4 (2) ◽  
pp. 119-128 ◽  
Author(s):  
R J Johnson ◽  
J Floege ◽  
W G Couser ◽  
C E Alpers
Keyword(s):  
Cell Proliferation ◽  
Growth Factor ◽  
Mesangial Cell ◽  
Mesangial Cells ◽  
Glomerular Disease ◽  
Platelet Derived Growth Factor ◽  
Mesangial Cell Proliferation ◽  
Experimental Nephritis

An approach for establishing a role for a growth factor in glomerular disease is presented. Using platelet-derived growth factor (PDGF) as an example, there is strong evidence to support the hypothesis that PDGF is a mediator of mesangial cell proliferation in glomerulonephritis. This includes evidence that (1) PDGF is a mitogen for mesangial cells in culture; (2) PDGF is expressed in both experimental and human glomerulonephritis in which mesangial cell proliferation occurs; (3) infusion of PDGF into rats induces mesangial cell proliferation and a hypercellular lesion; and (4) inhibition of PDGF in a model of experimental nephritis significantly reduces the mesangial cell proliferation. However, these data do not answer the question of whether or not the inhibition of PDGF in human diseases would be beneficial in the long term, because some cell proliferation is likely required for normal healing and repair. Further studies will be necessary to resolve this issue.

Suppression of Mesangial-Cell Proliferation by Trapidil in Glomerulonephritis Induced by Anti-Thymocyte Serum in Rats

1995 ◽  
Vol 23 (6) ◽  
pp. 458-466 ◽  
Author(s):  
M S Razzaque ◽  
M Cheng ◽  
T Taguchi
Keyword(s):  
Cell Proliferation ◽  
Body Weight ◽  
Single Dose ◽  
Growth Factor ◽  
Mesangial Cell ◽  
Platelet Derived Growth Factor ◽  
Group Iii ◽  
Group I ◽  
Mesangial Cell Proliferation ◽  
Group Ii

Trapadil (Mochida Pharmaceuticals, Japan), an antiplatelet drug, suppresses the growth of several cell types and is thought to antagonize platelet-derived growth factor. The effects of trapidil on mesangial-cell proliferation in glomerulonephritis induced by anti-thymocyte serum in Wistar rats were investigated. Control rats were treated with phosphate-buffered saline (group I); group II rats were injected with a single dose of anti-thymocyte serum (8 ml/kg body weight), and group III rats were treated with both a single dose of anti-thymocyte serum (8 ml/kg body weight) and with trapidil (5 mg/kg body weight/day). Three rats in each group were killed on day 3, and the other three on day 10. Control rats showed no significant histological changes on day 3 or day 10. In group II, on day 3, there was a marked decrease in glomerular cell numbers, with mesangiolysis. Histologically severe mesangial-cell proliferation with expansion of mesangial areas was noted on day 10. None of the rats in group III showed mesangial alterations, histologically, indicating that mesangial-cell proliferation was suppressed by trapidil. This suppression may result from antagonism of the binding of platelet derived growth factor to the specific surface receptors in the mesangial cells. Trapidil may have clinical value in the treatment of mesangial-cell proliferative glomerular diseases.

scholarly journals Inhibition of mesangial cell proliferation and matrix expansion in glomerulonephritis in the rat by antibody to platelet-derived growth factor.

1992 ◽  
Vol 175 (5) ◽  
pp. 1413-1416 ◽  
Author(s):  
R J Johnson ◽  
E W Raines ◽  
J Floege ◽  
A Yoshimura ◽  
P Pritzl ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Cell Proliferation ◽  
Growth Factor ◽  
Wound Repair ◽  
Mesangial Cell ◽  
Platelet Derived Growth Factor ◽  
Inflammatory Conditions ◽  
Mesangial Cell Proliferation ◽  
Matrix Expansion

Platelet-derived growth factor (PDGF), a potent mitogen for mesenchymal cells in culture, is expressed in vivo in a variety of inflammatory conditions associated with cell proliferation, including atherosclerosis, wound repair, pulmonary fibrosis, and glomerulonephritis. However, it is not known if PDGF mediates the fibroproliferative responses that characterize these inflammatory disorders. We administered neutralizing anti-PDGF IgG or control IgG to rats with mesangial proliferative nephritis. Inhibition of PDGF resulted in a significant reduction in mesangial cell proliferation, and largely prevented the increased deposition of extracellular matrix associated with the disease. This suggests that PDGF may have a central role in proliferative glomerular disease.

Interactions of Hydrogen Peroxide with Interleukin-6 and Platelet-Derived Growth Factor in Determining Mesangial Cell Growth: Effect of Repeated Oxidant Stress

1993 ◽  
Vol 85 (6) ◽  
pp. 747-751 ◽  
Author(s):  
R. J. D'Souza ◽  
H. M. Phillips ◽  
P. W. Jones ◽  
R. C. Strange ◽  
G. M. Aber
Keyword(s):  
Cell Proliferation ◽  
Growth Factor ◽  
Interleukin 6 ◽  
Mesangial Cell ◽  
Thymidine Incorporation ◽  
Mesangial Cells ◽  
Platelet Derived Growth Factor ◽  
Growth Effect ◽  
Cell Counts ◽  
Mesangial Cell Proliferation

1. This study examined the influence of H2O2, interleukin-6 and platelet-derived growth factor on the proliferation of rat mesangial cells. Mesangial cells were exposed to either a single pulse or three daily pulses of H2O2 (10−8-10−4 mol/l), alone or in combination with interleukin-6 (5 ng/ml) and/or platelet-derived growth factor (10 ng/ml). Proliferation was assessed after 24 h and 72 h of incubation using [3H]thymidine incorporation and cell counts. 2. Although one pulse of H2O2 had no significant effect on mesangial cell proliferation, three daily pulses of 10−6 mol/l H2O2 resulted in a significant increase in [3H]thymidine incorporation of 31 (52.6, 10.3)% (median and 75th-25th interquartile range) (P <0.001). Both interleukin-6 and platelet-derived growth factor were also mitogenic to mesangial cells, [3H]thymidine incorporation increasing by 19 (36.7, −6.7)% (P <0.05) and 53.5 (107, 21.9)% (P <0.001), respectively. The mitogenic effect of interleukin-6 was enhanced by 10−6 mol/l H2O2 [49.9 (77.7, 12.3)%] (P <0.01), whereas the addition of 10−6 mol/l H2O2 to platelet-derived growth factor resulted in a summated increase in [3H]thymidine incorporation of 82.7 (113, 57.4)% (P <0.001). Incubation with all three substances simultaneously resulted in down-regulation of growth compared with H2O2 plus platelet-derived growth factor by 55.4 (77.7, 103)% (P <0.05). 3. These findings suggest that reactive oxygen species may play a major role in determining the mesangial cell proliferation that occurs in certain forms of glomerulonephritis, acting either alone or in combination with other growth factors.

Sign in / Sign up

Export Citation Format

Share Document