Suramin Attenuates Renal Fibrosis The remnant kidney after 5/6 nephrectomy is a classic model that mostly mimics CKD in humans [14,15]. Histological studies of remnant kidney tissue have indicated a complex response consisting primarily of three steps: a hypertrophic phase, a quiescent phase with minimal histological alterations, and finally the development of segmental glomerular sclerosis and tubuloin- terstitial fibrosis [16,17]. Hyperfiltration has been identified as a significant contributor to the hypertrophy and glomerulosclerosis and macrophages play a key role in renal injury induced by glomerular hyperfiltration following reduction of kidney mass by ablation [18]. Macrophages localize to glomeruli and the interstitium via interactions with several chemokines, including monocyte chemo attractant protein-1(MCP-1), and regulated upon activation, normal upon expression normal T cell expressed and secreted (RANTES) [18,19,20]. This proinflammatory microenvironment promotes renal scarring [14,15]. In the kidney, tubular epithelial cells are considered to be a prominent source of chemokines [21]. MCP-1 and RANTES are two key chemokines that recruit monocytes/macrophages to the kidney [22,23]. Many mediators, including transformation growth factor-beta1 (TGF-beta1), epidermal growth factor (EGF), and platelet-derived growth factor (PDGF), are also upregulated in glomeruli and tubules and are believed to be involved in the progression of glomerular sclerosis and tubulointerstitial fibrosis [24,25,26]. The interaction of cytokines/growth factors with their receptors initiates different signaling pathways, leading to the activation of multiple transcrip- tional factors such as NF-kappaB and signal transducer and activator of transcription 3 (STAT3) that regulate various genes related to the activation of renal fibroblasts and initiation of inflammation [27]. In addition, activation of smad3, a key intracellular mediator in TGF-beta signaling, is induced in different models of renal fibrosis [12]. Recently, we have shown that suramin treatment can block phosphorylation of EGF receptor (EGFR), PDGF receptor (PDGFR), and smad3, However, it is unknown whether suramin is able to interfere with those signaling pathways and inactivation of NF-kappaB in the remnant kidney. In this study, we examined the effect of suramin on glomerular and vascular sclerosis, and inflammatory cell infiltration in the remnant kidney model. Further, we investigated the effect of suramin on the expression of MCP-1 and RANTES and the activation of growth factor receptors/intracellular signaling path- ways associated with the development of progressive renal injury. Figure 1. Effect of suramin on glomerular sclerosis in rat remnant kidney. (A) Photomicrographs Photomicrographys (4006) illustrating periodic acid-Schiff-stained sections of kidney tissue on week 4 after various treatments as indicated. (B) Photomicrographs (4006) illustrating trichrome stained kidney tissue on week 4 after various treatments. RK, remnant kidney. doi:10.1371/journal.pone.0036194.g001 PLoS ONE | www.plosone.org 2 April 2012 | Volume 7 | Issue 4 | e36194