Suramin Attenuates Renal Fibrosis Figure 8. Effect of suramin on phosphorylation of PDGF receptor and EGF receptor in rat remnant kidney. (A) Kidney tissue lysates were subjected to immunoblot analysis with specific antibodies against phospho-PDGF receptor-beta (p-PDGFR-beta), PDGF receptor, phospho-EGF receptor (p-EGFR), EGF receptor (EGFR). Expression levels of p-PDGFR-beta(B), PDGFR-beta (C), p-EGFR (D), EGFR (E) were quantified by densitometry and normalized with GAPDH. Data are represented as the mean 6 S.E.M (n = 6). Means with different superscript letters are significantly different from one another (P,0.05). doi:10.1371/journal.pone.0036194.g008 strongly associated with differentiation of renal fibroblasts to myofibroblasts, resulting in the production of excessive amount of ECM proteins [52]. Thus, interference with these receptors by suramin and subsequent blockade of signaling pathways initiated from these receptors may be an important mechanism in inhibiting renal fibroblast activation and attenuating production of ECM proteins. Our studies in this model clearly demonstrated that suramin treatment can abrogate phosphorylation of EGF and PDGF receptors and reduce phosphorylation of Smad-3, a key intracellular signaling molecule, downstream of TGF-betarecep- tors, supporting its inhibitory effect on multiple profibrotic receptors. These results are consistent with our observation in the UUO model [12], providing a strong rationale to develop suramin as a therapeutic intervention for fibrotic kidney disease. Suramin has been used to treat selected malignancies and metastatic diseases Our previous and current studies reveal that suramin administration can attenuate interstitial fibrosis, reduce glomerular and vascular injury, improve renal function and reduce proteinuria [12]. Further, delayed administration of suramin was also effective in attenuating the progression of renal fibrosis in obstructive nephropathy [13]. Therefore, there is the potential clinical application of suramin as an anti-fibrotic treatment in patients with chronic kidney disease. As suramin is already approved for use in humans, it would be possible to use it in clinical studies in CKD to test its efficacy and safety in patients with chronic kidney injury. In summary, we have shown that suramin inhibits glomerular and vascular sclerosis. The beneficial effects of suramin are linked PLoS ONE | www.plosone.org 8 April 2012 | Volume 7 | Issue 4 | e36194