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-(3Ј-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, suramininduced outgrowth, scattering, and proliferation of RPTC are through Src-mediated activation of the PI3K pathway but not ERK1/2 or the EGF receptor.

Recovery from Glycerol-Induced Acute Kidney Injury Is Accelerated by Suramin

“…This effect of suramin on TGF-␤ 1 was associated with decreased apoptosis 48 h after glycerol treatment and increased proximal tubular cellular proliferation. This finding is consistent with our previous data showing that TGF-␤ 1 induces apoptosis in renal proximal tubular cells and that suramin stimulates the proliferation of renal proximal tubular cells in primary cultures by activating the Src/Phosphoinositide 3-kinase/Protein kinase B pathway (Zhuang and Schnellmann, 2005).…”

“…Recently, it was reported that the delayed administration of suramin, a polysulfonated naphthylurea used in humans to treat trypanosomiasis, accelerates recovery from renal dysfunction induced by ischemia/reperfusion (I/R) injury, renal fibrosis, and obstructive nephropathies in mice (Zhuang and Schnellmann, 2005;Zhuang et al, 2009;Liu et al, 2011a,b). The mechanisms by which suramin accelerates recovery from renal dysfunction in these models remain incompletely understood but may be associated with the inhibition of apoptosis, suppression of inflammatory cytokine production, and promotion of epithelial cell proliferation.…”

Angiotensin II-Induced Cyclooxygenase 2 Expression in Rat Aorta Vascular Smooth Muscle Cells Does Not Require Heterotrimeric G Protein Activation

“…The ability of suramin to block G protein-dependent signaling pathways has led to many studies documenting its anticancer effects. However, recent evidence suggests that suramin, in certain cell types such as Chinese hamster ovary cells and renal epithelial cells, may actually activate signaling pathways related to cell proliferation (Nakata, 2004;Zhuang and Schnellmann, 2005). In the present study, treatment of cells with suramin did not alter surface expression of AT 1A Rs, AngII-induced AT 1A R trafficking, p42/44 ERK activation, or COX-2 expression.…”

Inhibition of Endosome-Lysosome System Acidification Enhances Porcine Circovirus 2 Infection of Porcine Epithelial Cells

“…Surprisingly, suramin, which causes intracellular vesicular swelling and decreases intralysosomal proteolysis (7,8,26,27,29), slightly increased PCV2 infection of epithelial cells. Another suramin activity may be responsible for the enhanced PCV2 infection, such as the activation of DNA synthesis (53,71), since PCV2 replication is cell cycle dependent and the stimulation of cellular proliferation by suramin may help PCV2 to replicate.…”