Endothelial to Mesenchymal Transition compromises vascular integrity to induce hypoxia and Myc mediated metabolic reprogramming of tubular epithelial cells in kidney fibrosis

The aim of this study was to identify the functional impact of Endothelial-to-Mesenchymal Transition (EndMT) in kidney fibrosis. For this purpose EndMT has been conditionally deleted in endothelial cells by the genetic deletion of Twist and Snail in the endothelial cells, using the tamoxifen inducible Cdh5-ERT2 Cre model. Twist EndMT–cKO and Snail EndMT–cKO mice, together with WT mice, were challanged with the unilateral ureteral obstruction model (UUO) to induce kidney fibrosis. Mice were euthanized 10 days after surgery. In addition, since we found that EndMT-induced vascular damage and hypoxia induces Myc upregulation in tubular epithelial cells (TECs), we deleted Myc in TECs (using the GGT-Cre model). Myc GGT–cKO mice were also challenged with the UUO model and euthanized 10 days after surgery. Transcriptional profile of fibrotic (UUO), healthy or contralateral kidneys from Twist, Snail and Myc conditional knock-out mice (triplicate for each experimental condition) was generated by whole transcriptome RNA-Seq using the Illumina platform.