Wnt/β-catenin signaling in kidney injury and repair: a double-edged sword

The Wnt/beta-catenin signaling cascade is an evolutionarily conserved, highly complex pathway that is known to be involved in kidney injury and repair after a wide variety of insults. Although the kidney displays an impressive ability to repair and recover after injury, these repair mechanisms can be overwhelmed, leading to maladaptive responses and eventual development of chronic kidney disease (CKD). Emerging evidence demonstrates that Wnt/beta-catenin signaling possesses dual roles in promoting repair/regeneration or facilitating progression to CKD after acute kidney injury (AKI), depending on the magnitude and duration of its activation. In this review, we summarize the expression, intracellular modification, and secretion of Wnt family proteins and their regulation in a variety of kidney diseases. We also explore our current understanding of the potential mechanisms by which transient Wnt/beta-catenin activation positively regulates adaptive responses of the kidney after AKI, and discuss how sustained activation of this signaling triggers maladaptive responses and causes destructive outcomes. A better understanding of these mechanisms may offer important opportunities for designing targeted therapy to promote adaptive kidney repair/recovery and prevent progression to CKD in patients.