PT  - JOURNAL ARTICLE
AU  - Zhuang, Shougang
AU  - Schnellmann, Rick G.
TI  - Suramin Promotes Proliferation and Scattering of Renal Epithelial Cells
AID  - 10.1124/jpet.104.080648
DP  - 2005 Jul 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 383--390
VI  - 314
IP  - 1
4099  - http://jpet.aspetjournals.org/content/314/1/383.short
4100  - http://jpet.aspetjournals.org/content/314/1/383.full
SO  - J Pharmacol Exp Ther2005 Jul 01; 314
AB  - 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. The American Society for Pharmacology and Experimental Therapeutics