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

التفاصيل البيبلوغرافية
العنوان: Human bone morphogenetic protein-7 does not counteract aristolochic acid-induced renal toxicity
المؤلفون: Marie-Françoise Bourgeade, Cécile Husson, Julie Piccirilli, Anne-Emilie Decleves, Frédéric Debelle, Fadoua El Kaddouri, Marie-Hélène Antoine, Frédérique Mies, Joëlle Nortier, Eric De Prez
المصدر: Journal of Applied Toxicology. 35:1520-1530
بيانات النشر: Wiley, 2015.
سنة النشر: 2015
مصطلحات موضوعية: medicine.medical_specialty, Aristolochic acid, Biology, Toxicology, Bone morphogenetic protein, medicine.disease, Nephrotoxicity, Nephropathy, Bone morphogenetic protein 7, chemistry.chemical_compound, Endocrinology, chemistry, In vivo, Internal medicine, Toxicity, medicine, Renal fibrosis
الوصف: 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 35 days (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. Copyright © 2015 John Wiley & Sons, Ltd.
تدمد: 0260-437X
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::6a111651553e47cae5cc838718d9e515Test
https://doi.org/10.1002/jat.3116Test
حقوق: CLOSED
رقم الانضمام: edsair.doi...........6a111651553e47cae5cc838718d9e515
قاعدة البيانات: OpenAIRE