Suramin promotes proliferation and scattering of renal epithelial cells.
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.
Zhuang
Shougang
S
Department of Pharmaceutical Sciences, Medical University of South Carolina, 280 Calhoun Street, Charleston, SC 29425, USA.
Schnellmann
Rick G
RG
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*
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