Apports de la protéomique quantitative différentielle haut-débit à l'étude des mécanismes de modification du cytosquelette de cellules tubulaires proximales induits par les Inhibiteurs de la Calcineurine

Abstract : In solid organ transplantation, Calcineurin Inhibitors, Cyclosporin A and Tacrolimus, prevent allograft rejection and ensure short-term allograft survival. However, CNI elicit nephrotoxic side effects whose mechanisms remain widely unsolved and are thought to participate to the multifactorial development of chronic kidney disease, leading to renal failure. The aim of thiswork was to combine targeted and untargeted experimental strategies to better understand CNI-induced physiopathological mechanisms.The first approach was based on the untargeted monitoring of the proximal tubular proteome by the quantitative shotgun proteomic technique, iTRAQ (« isobaric Tags for Relative & Absolute Quantitation »). The second approach consisted in the study of the Actin cytoskeleton of proximal tubular cells by classical molecular biology techniques. In the light of results from both approaches, this work reported that the Actin cytoskeleton of proximal tubular cells may play a part in the pathophysiology of CsA thanks to a mechanism based on an original regulation of the intracellular dynamics of Actin.
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Bastien Burat. Apports de la protéomique quantitative différentielle haut-débit à l'étude des mécanismes de modification du cytosquelette de cellules tubulaires proximales induits par les Inhibiteurs de la Calcineurine. Biologie moléculaire. Université de Limoges, 2017. Français. ⟨NNT : 2017LIMO0104⟩. ⟨tel-01720027⟩

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