title: Suramin promotes proliferation and scattering of renal epithelial cells.
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.
authors.affiliation: Department of Pharmaceutical Sciences, Medical University of South Carolina, 280 Calhoun Street, Charleston, SC 29425, USA.
authors.forename: Shougang
authors.initials: S
authors.lastname: Zhuang
authors.forename: Rick G
authors.initials: RG
authors.lastname: Schnellmann
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D004815:Epidermal Growth Factor / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects*; D005260:Female; D016391:Genes, src / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D007202:Indicators and Reagents; D007668:Kidney / Q000166:cytology* / Q000187:drug effects; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000187:drug effects; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011817:Rabbits; D015398:Signal Transduction / Q000187:drug effects; D013498:Suramin / Q000494:pharmacology*; D013778:Tetrazolium Salts; D013844:Thiazoles; D014344:Trypanocidal Agents / Q000494:pharmacology*
chemical_list: D007202:Indicators and Reagents; D013778:Tetrazolium Salts; D013844:Thiazoles; D014344:Trypanocidal Agents; D013498:Suramin; D004815:Epidermal Growth Factor; D019869:Phosphatidylinositol 3-Kinases; C022616:thiazolyl blue