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      Effect of the Platelet-Derived Growth Factor Antagonist Trapidil on Mesangial Cell Proliferation in Rats

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          Platelet-derived growth factor (PDGF) is known as a potent mediator in the proliferation of mesangial cells in culture and in mesangial proliferative nephritis. The present study was undertaken to evaluate the effect of trapidil, an antagonist of PDGF, on mesangial cell proliferation in culture and in anti-Thy-1.1 nephritis in rats. Trapidil significantly inhibited <sup>3</sup>H-thymidine incorporation in the mesangial cells stimulated by PDGF BB and suppressed mesangial cell proliferation in culture in a dose-dependent manner. In anti-Thy-1.1 nephritis, a significant reduction in the number of total glomerular cells and also proliferating (proliferating cell nuclear antigen positive) cells was demonstrated on day 7 in the rats treated with trapidil as compared with controls. Although renal function expressed as blood urea nitrogen and creatinine levels did not differ between rats with and without trapidil treatment, the present results suggest a salutary effect of trapidil on mesangial cell proliferation. PDGF, therefore, could play an important role in mediating mesangial cell proliferation.

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          Cyclin/PCNA is the auxiliary protein of DNA polymerase-delta.

          Identification of the cellular proteins whose expression is regulated during the cell cycle in normal cells is essential for understanding the mechanisms involved in the control of cell proliferation. A nuclear protein called cyclin of relative molecular mass 36,000 (Mr 36K), whose synthesis correlates with the proliferative state of the cell, has been identified in several cell types of human, mouse, hamster and avian origin. The rate of cyclin synthesis is very low in quiescent cells and increases several fold after serum stimulation shortly before DNA synthesis. Immunofluorescence and autoradiography studies have shown that the nuclear staining patterns of cyclin during S phase have a sequential order of appearance and a clear correlation can be found between DNA synthesis and cyclin positive nuclei. The proliferating cell nuclear antigen (PCNA) and cyclin have many common properties and it has been shown that these two are identical. Recently a protein which is required by DNA polymerase-delta for its catalytic activity with templates having low primer/template ratios has been isolated from calf thymus. We report here that cyclin and the auxiliary protein of DNA polymerase-delta are identical.
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            A new approach to the treatment of atherosclerosis and trapidil as an antagonist to platelet-derived growth factor


              Author and article information

              S. Karger AG
              April 1999
              31 March 1999
              : 81
              : 4
              : 428-433
              a2nd Department of Internal Medicine, Toyama Medical and Pharmaceutical University, and bDepartment of Internal Medicine, Toyama Prefectural Central Hospital, Toyama, Japan
              45327 Nephron 1999;81:428–433
              © 1999 S. Karger AG, Basel

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              Page count
              Figures: 4, Tables: 1, References: 25, Pages: 6
              Self URI (application/pdf): https://www.karger.com/Article/Pdf/45327
              Original Paper


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