Effects of MCP-1 inhibition by bindarit therapy in a rat model of polycystic kidney disease

Carlamaria Zoja, Daniela Corna, Monica Locatelli, Daniela Rottoli, Anna Pezzotta, Marina Morigi, Cristina Zanchi, Simona Buelli, Angelo Guglielmotti, Norberto Perico, Andrea Remuzzi, Giuseppe Remuzzi

Research output: Contribution to journalArticle

Abstract

Background/Aims: Experimental and clinical evidence suggested that monocyte chemoattractant protein-1 (MCP-1/CCL2) has a role in the development of interstitial inflammation and renal failure in polycystic kidney disease (PKD). We investigated whether bindarit, an inhibitor of MCP-1/CCL2 synthesis, could influence the evolution of PKD in PCK rats. Methods: PCK rats were treated from 5 to 15 weeks of age with vehicle or bindarit. Sprague-Dawley rats served as control. For in vitro studies, murine podocytes were exposed to albumin with or without bindarit. Results: MCP-1 mRNA was upregulated in the kidney of PCK rats and reduced by bindarit. Treatment limited overexpression of MCP-1 protein by epithelial cells of dilated tubules and cysts, and interstitial inflammatory cells. Excessive renal accumulation of mono-cytes/macrophages was lowered by bindarit by 41%. Serum creatinine slightly increased in PCK rats on vehicle and was similar to controls after bindarit. Kidney and liver cysts were not affected by treatment. Bindarit significantly reduced progressive proteinuria of PCK rats. The antiproteinuric effect was associated with the restoration of the defective nephrin expression in podocytes of PCK rats. Bindarit limited podocyte foot process effacement and ameliorated slit diaphragm frequency. In cultured podocytes, bindarit reduced MCP-1 production in response to albumin and inhibited albumin-induced cytoskeletal remodeling and cell migration. Conclusion: This study showed that although bindarit did not prevent renal cyst growth, it limited interstitial inflammation and renal dysfunction and reduced proteinuria in PKD. Thus, bindarit could be considered a therapeutic intervention complementary to therapies specifically acting to block renal cyst growth.

Original languageEnglish
Pages (from-to)52-61
Number of pages10
JournalNephron
Volume129
Issue number1
DOIs
Publication statusPublished - Jan 1 2015

    Fingerprint

Keywords

  • Bindarit
  • Interstitial inflammation
  • MCP-1
  • PCK rat
  • Podocyte
  • Polycystic kidney disease
  • Proteinuria

ASJC Scopus subject areas

  • Physiology
  • Nephrology
  • Urology
  • Physiology (medical)
  • Medicine(all)

Cite this