RNA-seq analysis of dickkopf-3 knockout and C57Bl/6 mice kidneys 7 days after unilateral ureteral obstruction. Mus musculus

Renal tubular atrophy and interstitial fibrosis are common hallmarks of etiologically different progressive chronic kidney diseases (CKD) that eventually result in organ failure. We identify Dickkopf-3 (Dkk3) as a stress-induced, tubular epithelia-derived mediator of kidney fibrosis. Genetic as well as antibody-mediated abrogation of Dkk3 led to reduced tubular atrophy and decreased interstitial matrix accumulation in two mouse models of renal fibrosis. This was accompanied by an amplified, anti-fibrogenic, inflammatory response within the injured kidney. Mechanistically, Dkk3 deficiency led to diminished canonical Wnt/β-catenin signaling in stressed tubular epithelial cells. To identify global changes in gene expression due to the lack of Dkk3, whole-transcriptome sequencing (mRNA-seq) was performed on RNA isolated from kidneys of Wt and Dkk3-/- mice 7 days after UUO. Overall design: Kidneys of Dkk3-/- and C57Bl/6 mice were harvested 7 days after UUO. Total RNA was isolated and each Sample was prepared as a 10-plex, which was sequenced on three lanes. HiSeq 2000 50bp SR run was used.