Direct effects of simvastatin on proliferation and matrix accumulation in cultured murine mesangial cells

被引：1

作者：

Nogaki F. ^{[1
]}

Muso E. ^{[1
]}

Yashiro M. ^{[2
]}

Kasuno K. ^{[1
]}

Kamata T. ^{[3
]}

Ono T. ^{[1
]}

Sasayama S. ^{[1
]}

机构：

[1] Department of Cardiovascular Medicine, Kyoto University, Graduate School of Medicine, Shogoin, Sakyo-ku, Kyoto 606-8397

[2] Kyoto City Hospital, Kyoto

[3] Himeji National Hospital, Himeji

来源：

Clinical and Experimental Nephrology | 2001年 / 5卷 / 2期

关键词：

Collagen type IV; Mesangial cells; Plasminogen activator inhibitor-1; Platelet-derived growth factor; Simvastatin;

D O I：

10.1007/s101570170015

中图分类号：

学科分类号：

摘要：

Background. 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors have been demonstrated to suppress glomerular injuries in various renal diseases. However, it is not fully clear whether HMG-CoA reductase inhibitors directly regulate matrix protein accumulation in mesangial cells. Methods. We investigated the effect of simvastatin (SIM), an HMG-CoA reductase inhibitor, on DNA synthesis in cultured murine mesangial cells stimulated by fetal calf serum (FCS). We then determined whether SIM affected the expression of regulatory factors of cell growth and matrix protein accumulation, using Northern analysis. Results. SIM dose-dependently inhibited FCS-induced DNA synthesis after 24 h of incubation. SIM treatment for 24 h suppressed the mRNA expression of platelet-derived growth factor (PDGF)-B chain, PDGF receptor β-subunit and c-myc, while the expression of transforming growth factor β (TGF-β) was not affected. Concerning matrix protein synthesis, the mRNA expression of type IV collagen was suppressed, whereas that of type III collagen was markedly upregulated. As for matrix turnover proteins, SIM had a markedly suppressive effect on the mRNA expression of plasminogen activator inhibitor-1 (PAI-1), with a constant expression of tissue-type plasminogen activator (tPA). Conclusions. These results indicate that SIM may suppress mesangial cell proliferation in part through the downregulation of PDGF, PDGF-receptor, and c-myc mRNA expressions. In addition, the suppression of the synthesis of collagen IV and PAI-1 appears to be a direct inhibitory effect of SIM on glomerular matrix accumulation.

引用

页码：85 / 89

页数：4

共 29 条

[1]

Keane W.F., Kasiske B.L., O'Donnell M.P., Lipids and progressive glomerulosclerosis, Am J Nephrol, 8, pp. 261-271, (1988)

[2]

Diamond J.R., Karnovsky M.J., Focal and segmental glomerulosclerosis: Analogies to atherosclerosis, Kidney Int, 33, pp. 917-924, (1988)

[3]

Kasiske B.L., O'Donnell M.P., Cleary M.P., Keane W.F., Treatment of hyperlipidemia reduces glomerular injury in obese Zucker rats, Kidney Int, 33, pp. 667-672, (1988)

[4]

Kasiske B.L., O'Donnell M.P., Gravis W.J., Keane W.F., Pharmacologic treatment of hyperlipidemia reduces glomerular injury in rat 5/6 nephrectomy model of chronic renal failure, Circ Res, 62, pp. 367-374, (1988)

[5]

Muso E., Yashiro M., Matsushima M., Yoshida H., Does LDL-apheresis in steroid-resistant nephrotic syndrome affect prognosis?, Nephrol Dial Transplant, 9, pp. 257-264, (1994)

[6]

O'Donnell M.P., Kasiske B.L., Kim Y., Schmitz P.G., Keane W.F., Lovastatin retards the progression of established glomerular disease in obese Zucker rats, Am J Kidney Dis, 22, pp. 83-89, (1993)

[7]

Kim S.B., Kang S.A., Cho Y.J., Park S.K., Cheong H.I., Lee J.D., Et al., Effects of low density lipoprotein on type IV collagen production by cultured rat mesangial cells, Nephron, 67, pp. 327-333, (1994)

[8]

Rovin B.H., Tan L.C., LDL stimulates mesangial fibronectin production and chemoattractant expression, Kidney Int, 43, pp. 218-225, (1993)

[9]

Coritsidis G., Rifici V., Gupta S., Rie J., Shan Z.H., Neugarten J., Et al., Preferential binding of oxidized LDL to rat glomeruli in vivo and cultured mesangial cells in vitro, Kidney Int, 39, pp. 858-866, (1991)

[10]

Vincent T.S., Wulfert E., Merler E., Inhibition of growth factor signaling pathways by lovastatin, Biochem Biophys Res Commun, 180, pp. 1284-1289, (1991)

← 1 2 3 →