Dipyridamole inhibits human mesangial cell proliferation

G S Hillis, L A Duthie, A M MacLeod

    Research output: Contribution to journalArticle

    16 Citations (Scopus)

    Abstract

    Background: Many glomerular diseases are associated with mesangial cell proliferation and the accumulation of extracellular matrix. At present, there are, however, few treatments which can inhibit these processes. The current study assessed the effects of the anti-platelet and putative anti-proliferative drug dipyridamole (DP) on the growth of human mesangial cells in vitro and their production of the extracellular matrix protein, fibronectin. Methods: Human mesangial cell proliferation, both intrinsic and stimulated by platelet-derived growth factor, was assessed using H-3-thymidine incorporation and an MTT proliferation assay. A sandwich enzyme-linked immunosorbent assay was used to study the effects of DP on fibronectin synthesis, again in cells stimulated by transforming growth factor beta 1 and in unstimulated cells. Results: At concentrations compatible with the serum levels found in subjects consuming standard dosages, DP significantly inhibited the growth of human mesangial cells in vitro in a dose-dependent fashion. DP also abrogated the mitogenic effects of platelet-derived growth factor. It had no significant effects on the synthesis of fibronectin by these cells (either spontaneous or induced by transforming growth factor beta 1). There was no evidence of cytotoxicity. Conclusion: These data suggest that DP may have a therapeutic role in proliferative glomerulonephritis and possibly other diseases characterized by cell proliferation.

    Original languageEnglish
    Pages (from-to)172-178
    Number of pages7
    JournalNephron Experimental Nephrology
    Volume78
    Issue number2
    Publication statusPublished - Feb 1998

    Keywords

    • dipyridamole
    • mesangial cell
    • cell proliferation
    • fibronectin
    • MONOCLONAL-ANTIBODIES
    • EXTRACELLULAR-MATRIX
    • GROWTH-FACTOR
    • GLOMERULONEPHRITIS
    • PROGRESSION
    • FIBROSIS
    • DISEASE
    • THERAPY
    • CULTURE

    Cite this

    Hillis, G. S., Duthie, L. A., & MacLeod, A. M. (1998). Dipyridamole inhibits human mesangial cell proliferation. Nephron Experimental Nephrology, 78(2), 172-178.

    Dipyridamole inhibits human mesangial cell proliferation. / Hillis, G S ; Duthie, L A ; MacLeod, A M .

    In: Nephron Experimental Nephrology, Vol. 78, No. 2, 02.1998, p. 172-178.

    Research output: Contribution to journalArticle

    Hillis, GS, Duthie, LA & MacLeod, AM 1998, 'Dipyridamole inhibits human mesangial cell proliferation', Nephron Experimental Nephrology, vol. 78, no. 2, pp. 172-178.
    Hillis GS, Duthie LA, MacLeod AM. Dipyridamole inhibits human mesangial cell proliferation. Nephron Experimental Nephrology. 1998 Feb;78(2):172-178.
    Hillis, G S ; Duthie, L A ; MacLeod, A M . / Dipyridamole inhibits human mesangial cell proliferation. In: Nephron Experimental Nephrology. 1998 ; Vol. 78, No. 2. pp. 172-178.
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    abstract = "Background: Many glomerular diseases are associated with mesangial cell proliferation and the accumulation of extracellular matrix. At present, there are, however, few treatments which can inhibit these processes. The current study assessed the effects of the anti-platelet and putative anti-proliferative drug dipyridamole (DP) on the growth of human mesangial cells in vitro and their production of the extracellular matrix protein, fibronectin. Methods: Human mesangial cell proliferation, both intrinsic and stimulated by platelet-derived growth factor, was assessed using H-3-thymidine incorporation and an MTT proliferation assay. A sandwich enzyme-linked immunosorbent assay was used to study the effects of DP on fibronectin synthesis, again in cells stimulated by transforming growth factor beta 1 and in unstimulated cells. Results: At concentrations compatible with the serum levels found in subjects consuming standard dosages, DP significantly inhibited the growth of human mesangial cells in vitro in a dose-dependent fashion. DP also abrogated the mitogenic effects of platelet-derived growth factor. It had no significant effects on the synthesis of fibronectin by these cells (either spontaneous or induced by transforming growth factor beta 1). There was no evidence of cytotoxicity. Conclusion: These data suggest that DP may have a therapeutic role in proliferative glomerulonephritis and possibly other diseases characterized by cell proliferation.",
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    N2 - Background: Many glomerular diseases are associated with mesangial cell proliferation and the accumulation of extracellular matrix. At present, there are, however, few treatments which can inhibit these processes. The current study assessed the effects of the anti-platelet and putative anti-proliferative drug dipyridamole (DP) on the growth of human mesangial cells in vitro and their production of the extracellular matrix protein, fibronectin. Methods: Human mesangial cell proliferation, both intrinsic and stimulated by platelet-derived growth factor, was assessed using H-3-thymidine incorporation and an MTT proliferation assay. A sandwich enzyme-linked immunosorbent assay was used to study the effects of DP on fibronectin synthesis, again in cells stimulated by transforming growth factor beta 1 and in unstimulated cells. Results: At concentrations compatible with the serum levels found in subjects consuming standard dosages, DP significantly inhibited the growth of human mesangial cells in vitro in a dose-dependent fashion. DP also abrogated the mitogenic effects of platelet-derived growth factor. It had no significant effects on the synthesis of fibronectin by these cells (either spontaneous or induced by transforming growth factor beta 1). There was no evidence of cytotoxicity. Conclusion: These data suggest that DP may have a therapeutic role in proliferative glomerulonephritis and possibly other diseases characterized by cell proliferation.

    AB - Background: Many glomerular diseases are associated with mesangial cell proliferation and the accumulation of extracellular matrix. At present, there are, however, few treatments which can inhibit these processes. The current study assessed the effects of the anti-platelet and putative anti-proliferative drug dipyridamole (DP) on the growth of human mesangial cells in vitro and their production of the extracellular matrix protein, fibronectin. Methods: Human mesangial cell proliferation, both intrinsic and stimulated by platelet-derived growth factor, was assessed using H-3-thymidine incorporation and an MTT proliferation assay. A sandwich enzyme-linked immunosorbent assay was used to study the effects of DP on fibronectin synthesis, again in cells stimulated by transforming growth factor beta 1 and in unstimulated cells. Results: At concentrations compatible with the serum levels found in subjects consuming standard dosages, DP significantly inhibited the growth of human mesangial cells in vitro in a dose-dependent fashion. DP also abrogated the mitogenic effects of platelet-derived growth factor. It had no significant effects on the synthesis of fibronectin by these cells (either spontaneous or induced by transforming growth factor beta 1). There was no evidence of cytotoxicity. Conclusion: These data suggest that DP may have a therapeutic role in proliferative glomerulonephritis and possibly other diseases characterized by cell proliferation.

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