Analysis of transcriptomic and proteomic profiles demonstrates improved Madin–Darby canine kidney cell function in a renal microfluidic biochip

Authors

  • Leila Choucha Snouber,

    1. CNRS UMR 6600, Laboratoire de Biomécanique et Bio Ingénierie, Université de Technologie de Compiègne, France
    Search for more papers by this author
  • Franck Letourneur,

    1. INSERM U1016, CNRS UMR 8104, Plate-forme Génomique Institut Cochin, Paris, France, Université Paris Descartes, Sorbonne Paris Cité, Paris, France
    Search for more papers by this author
  • Philippe Chafey,

    1. INSERM U1016, CNRS UMR 8104, Plate-forme Protéomique Institut Cochin, Paris, France, Université Paris Descartes, Sorbonne Paris Cité, Paris, France
    Search for more papers by this author
  • Cedric Broussard,

    1. INSERM U1016, CNRS UMR 8104, Plate-forme Protéomique Institut Cochin, Paris, France, Université Paris Descartes, Sorbonne Paris Cité, Paris, France
    Search for more papers by this author
  • Matthieu Monge,

    1. Nephrology Department, Leiden University Medical Center, Albinusdreef 2, 2333ZA Leiden, The Netherlands
    2. Service de Néphrologie et Médecine Interne, Centre Hospitalier Universitaire d'Amiens, 80054 Amiens, France
    Search for more papers by this author
  • Cécile Legallais,

    1. CNRS UMR 6600, Laboratoire de Biomécanique et Bio Ingénierie, Université de Technologie de Compiègne, France
    Search for more papers by this author
  • Eric Leclerc

    Corresponding author
    1. CNRS UMR 6600, Laboratoire de Biomécanique et Bio Ingénierie, Université de Technologie de Compiègne, France
    • CNRS UMR 6600, Laboratoire de Biomécanique et Bio Ingénierie, Université de Technologie de Compiègne, France
    Search for more papers by this author

Abstract

We have evaluated the influence of the microfluidic environment on renal cell functionality. For that purpose, we performed a time lapse transcriptomic and proteomic analysis in which we compared gene and protein expressions of Madin–Darby canine kidney cells after 24 h and 96 h of culture in both microfluidic biochips and plates. The transcriptomic and proteomic integration revealed that the ion transporters involved in calcium, phosphate, and sodium homoeostasis and several genes involved in H+ transporters and pH regulation were up-regulated in microfluidic biochips. Concerning drug metabolism, we found Phase I (CYP P450), Phase II enzymes (GST), various multidrug resistance genes (MRP), and Phase III transporters (SLC) were also up-regulated in the biochips. Furthermore, the study shows that those inductions were correlated with the induction of the Ahr and Nrf-2 dependent pathways, which results in a global cytoprotective response induced by the microenvironment. However, there was no apoptosis situation or cell death in the biochips. Microfluidic biochips may thus provide an important insight into exploring xenobiotic injury and transport modifications in this type of bioartificial microfluidic kidney. Finally, the investigation demonstrated that combining the transcriptomic and proteomic analyses obtained from a cell “on chip” culture would provide a pertinent new tool in the mechanistic interpretation of cellular mechanisms for predicting kidney cell toxicity and renal clearance in vitro. © 2011 American Institute of Chemical Engineers Biotechnol. Prog., 2012

Ancillary