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Gröne, Elisabeth F.; Federico, Giuseppina; Nelson, Peter J.; Arnold, Bernd; Gröne, Hermann-Josef (2017): The hormetic functions of Wnt pathways in tubular injury. In: Pflugers Archiv-European Journal of Physiology, Vol. 469, No. 43319: pp. 899-906
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Abstract

Chronic tubulointerstitial damage with tubular epithelial atrophy and interstitial fibrosis is the hallmark of chronic kidney disease (CKD) and a predictor for progression of CKD. Several experiments have now provided evidence that the Wnt signaling pathways are significantly contributing to atrophy and fibrosis;in contrast, it also has been shown that the Wnt system fosters regenerative processes in acute tubular injury. We now have demonstrated that Dickkopf 3 (DKK3) is an agonist for canonical Wnt signaling in CKD and fosters chronic fibrosing inflammation of the tubulointerstitial compartment. Genetic- and antibody-mediated inhibition of DKK3 leads to a pronounced improvement of tubular differentiation and a reduction in fibrosis. In addition, the secreted glycoprotein DKK3 can be used as a non-invasive urinary marker for the extent of CKD in man.