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Research ArticleGASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL

Suramin Promotes Proliferation and Scattering of Renal Epithelial Cells

Shougang Zhuang and Rick G. Schnellmann
Journal of Pharmacology and Experimental Therapeutics July 2005, 314 (1) 383-390; DOI: https://doi.org/10.1124/jpet.104.080648
Shougang Zhuang
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Rick G. Schnellmann
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Abstract

Primary cultures of renal proximal tubules are known to recapitulate several early events in the process of renal regeneration following injury. In this study, we show that suramin, a polysulfonated naphthylurea, stimulates outgrowth, scattering, and proliferation of primary cultures of renal proximal tubule cells (RPTC). These responses were comparable to those produced by epidermal growth factor (EGF). However, AG-1478 [4-(3′-chloroanilino)-6,7-dimethoxy-quinazoline], a specific inhibitor of the EGF receptor, blocked EGF but not suramin-induced RPTC outgrowth, scattering, and proliferation. Suramin stimulated phosphorylation of Akt, a downstream kinase of phosphoinositide 3-kinase (PI3K), extracellular signaling-regulated kinase 1/2 (ERK1/2), and Src, but not the EGF receptor. Blockade of Src, but not the EGF receptor, inhibited Akt and ERK1/2 phosphorylation. Furthermore, inactivation of PI3K with LY294002 [2-(4morpholinyl)-8-phenyl-4H-1-benzopyran-4-one] blocked suramin-induced RPTC outgrowth, scattering, and proliferation, whereas blockade of ERK1/2 had no effect. These data identify novel effects of suramin in RPTC outgrowth, scattering, and proliferation. Furthermore, suramin-induced outgrowth, scattering, and proliferation of RPTC are through Src-mediated activation of the PI3K pathway but not ERK1/2 or the EGF receptor.

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  • Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.

  • doi:10.1124/jpet.104.080648.

  • ABBREVIATIONS: EGF, epidermal growth factor; TGF, transforming growth factor; CHO, Chinese hamster ovary; PI3K, phosphoinositide 3-kinase; ERK, extracellular signaling-regulated kinase; RPTC, renal proximal tubular cell(s); LY294002, 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; U0126, 1,4-diamino-2,3-dicyano-1,4-bis(2-aminophenylthio)butadiene; AG-1478, 4-(3-chloroanilino)-6,7-dimethoxyquinazoline; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide; PP1, 4-amino-5-(4-methylphenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine; PTP, protein tyrosine phosphatase.

    • Received November 11, 2004.
    • Accepted April 12, 2005.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 381 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 381, Issue 2
1 May 2022
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Research ArticleGASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL

Suramin Promotes Proliferation and Scattering of Renal Epithelial Cells

Shougang Zhuang and Rick G. Schnellmann
Journal of Pharmacology and Experimental Therapeutics July 1, 2005, 314 (1) 383-390; DOI: https://doi.org/10.1124/jpet.104.080648

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Research ArticleGASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL

Suramin Promotes Proliferation and Scattering of Renal Epithelial Cells

Shougang Zhuang and Rick G. Schnellmann
Journal of Pharmacology and Experimental Therapeutics July 1, 2005, 314 (1) 383-390; DOI: https://doi.org/10.1124/jpet.104.080648
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