Human bone morphogenetic protein-7 does not counteract aristolochic acid-induced renal toxicity

Marie Hélène Antoine, Frédéric Debelle, Julie Piccirilli, Fadoua El Kaddouri, Anne Emilie Declèves, Eric De Prez, Cécile Husson, Frédérique Mies, Marie Françoise Bourgeade, Joëlle L. Nortier

Research output: Contribution to journalArticlepeer-review


Aristolochic acids (AA) are nephrotoxic and profibrotic agents, leading to chronic kidney disease. As some controversial studies have reported a nephroprotective effect of exogenous recombinant human bone morphogenetic protein (rhBMP)-7 in several models of renal fibrosis, we investigated the putative effect of rhBMP-7 to prevent progressive tubulointerstitial damage after AA intoxication in vitro and in vivo. In vitro, the toxicity of AA on renal tubular cells was demonstrated by an increase in vimentin as well as a decrease in β-catenin expressions, reflecting a dedifferentiation process. Increased fibronectin and interleukin-6 levels were measured in the supernatants. Enhanced α-SMA mRNA levels associated to decreased E-cadherin mRNA levels were also measured. Incubation with rhBMP-7 only prevented the increase in vimentin and the decrease in β-catenin expressions. In vivo, in a rat model of AA nephropathy, severe tubulointerstitial lesions induced by AA after 10 and 35days (collagen IV deposition and tubular atrophy), were not prevented by the rhBMP-7 treatment. Similarly, rhBMP-7 did not ameliorate the significant increase in urinary concentrations of transforming growth factor-β. In summary, our in vitro data demonstrated a poor beneficial effect of rhBMP-7 to reverse cell toxicity while, in vivo, there was no beneficial effect of rhBMP-7. Therefore, further investigations are needed to confirm the exact role of BMP-7 in progressive chronic kidney disease.

Original languageEnglish
Pages (from-to)1520-1530
Number of pages11
JournalJournal of Applied Toxicology
Issue number12
Publication statusPublished - 1 Dec 2015


  • Aristolochic acids
  • Bone morphogenetic protein-7
  • Proximal tubular epithelial cell
  • Renal fibrosis
  • Tubular cell dedifferentiation


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