New insights into the role and mechanism of Wnt/β‐catenin signalling in kidney fibrosis

ABSTRACT Wnt/β‐catenin is an evolutionarily conserved, developmental signalling pathway that regulates embryogenesis, injury repair and pathogenesis of human diseases. Dysregulated activation of Wnt/β‐catenin is associated with the development and progression of renal fibrotic lesions after injury. Wnt are induced and β‐catenin is activated in various models of experimental chronic kidney disease (CKD) and in human nephropathies. Recent findings indicate that pro(renin) receptor is an amplifier of Wnt/β‐catenin by acting as a downstream target and an obligatory component for its signal transduction. Genetic blockade of Wnt secretion in a cell type‐specific manner uncovers renal tubular epithelium as the major source of Wnt ligands in CKD. Wnt/β‐catenin controls the expression of a wide variety of downstream mediators implicated in kidney fibrosis, such as fibronectin, Snail1, matrix metalloproteinase‐7, hepatocyte growth factor and various components of the renin‐angiotensin system. Targeted inhibition of Wnt/β‐catenin is able to ameliorate kidney fibrotic lesions in pre‐clinical settings. In this review, we summarize recent advances in our understanding of the regulation, signal transduction, role and mechanisms of Wnt/β‐catenin signalling in the pathogenesis of kidney fibrosis. We also discuss the therapeutic potential of targeting this pathway for the treatment of fibrotic CKD.