Suramin Inhibits Renal Fibrosis in Chronic Kidney Disease

• Published in: Journal of the American Society of Nephrology Vol. 22; no. 6; pp. 1064 - 1075
• Main Authors: NA LIU, TOLBERT, Evelyn, MAOYIN PANG, PONNUSAMY, Murugavel, HAIDONG YAN, SHOUGANG ZHUANG
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society of Nephrology 01.06.2011
• Subjects: Actins - metabolism; Animals; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Basic Research; Biological and medical sciences; Cells, Cultured; Chronic Disease; Disease Models, Animal; Disease Progression; Fibroblasts - cytology; Fibroblasts - drug effects; Fibroblasts - metabolism; Fibronectins - metabolism; Fibrosis; Kidney - drug effects; Kidney - metabolism; Kidney - pathology; Kidney Diseases - drug therapy; Kidney Diseases - pathology; Kidneys; Male; Medical sciences; Mice; Mice, Inbred C57BL; Nephrology. Urinary tract diseases; Nephropathies. Renovascular diseases. Renal failure; Proteinuria - prevention & control; Rats; Rats, Sprague-Dawley; Renal failure; Smad Proteins - metabolism; Suramin - pharmacology; Suramin - therapeutic use; Transforming Growth Factor beta1 - metabolism; Transforming Growth Factor beta1 - pharmacology; Treatment Outcome; Urinary system involvement in other diseases. Miscellaneous; Kidney disease; Antiprotozoal agent; Nephrology; Urinary system disease; Renal failure; Parasiticide; Antiviral; Inhibitor; Chronic kidney disease; Suramin sodium; Urology
• ISSN: 1046-6673; 1533-3450
• DOI: 10.1681/ASN.2010090956

The activation of cytokine and growth factor receptors associates with the development and progression of renal fibrosis. Suramin is a compound that inhibits the interaction of several cytokines and growth factors with their receptors, but whether suramin inhibits the progression of renal fibrosis is unknown. Here, treatment of cultured renal interstitial fibroblasts with suramin inhibited their activation induced by TGF-β1 and serum. In a mouse model of obstructive nephropathy, administration of a single dose of suramin immediately after ureteral obstruction abolished the expression of fibronectin, largely suppressed expression of α-SMA and type I collagen, and reduced the deposition of extracellular matrix proteins. Suramin also decreased the expression of multiple cytokines including TGF-β1 and reduced the interstitial infiltration of leukocytes. Moreover, suramin decreased expression of the type II TGF-β receptor, blocked phosphorylation of the EGF and PDGF receptors, and inactivated several signaling pathways associated with the progression of renal fibrosis. In a rat model of CKD, suramin abrogated proteinuria, limited the decline of renal function, and prevented glomerular and tubulointerstitial damage. Collectively, these findings indicate that suramin is a potent antifibrotic agent that may have therapeutic potential for patients with fibrotic kidney diseases.