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/-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. SOURCE: Carsten Jäckel Klinikum der Universität München, Klinische Biochemie

Pluto Bioinformatics

GSE75925: RNA-seq analysis of dickkopf-3 knockout and C57Bl/6 mice kidneys 7 days after unilateral ureteral obstruction