Wnt6 regulates epithelial cell differentiation and is dysregulated in renal fibrosis.

Wnt6 regulates epithelial cell differentiation and is dysregulated in renal fibrosis. Am J Physiol Renal Physiol. 2016 Apr 27;:ajprenal.00136.2016 Authors: Beaton H, Andrews D, Parsons M, Murphy M, Gaffney A, Kavanagh D, McKay GJ, Maxwell AP, Taylor CT, Cummins EP, Godson C, Higgins DF, Murphy P, Crean J Abstract Diabetic nephropathy is the most common microvascular complication of diabetes mellitus, manifesting as mesangial expansion, glomerular basement membrane thickening, glomerular sclerosis and progressive tubulointerstitial fibrosis leading to end-stage renal disease. Here we describe the functional characterization of Wnt6, whose expression is progressively lost in diabetic nephropathy and animal models of acute tubular injury and renal fibrosis. We have shown prominent Wnt6 and FzD7 expression in the mesonephros of the developing mouse kidney, suggesting a role for Wnt6 in epithelialization. Importantly, TCF/Lef reporter activity is also prominent in the mesonephros. Analysis of Wnt family members in human renal biopsies identified differential expression of Wnt6, correlating with severity of the disease. In animal models of tubular injury and fibrosis, loss of Wnt6 was evident. Wnt6 signals through the canonical pathway in renal epithelial cells as evidenced by increased phosphorylation of GSK3β (Ser9), nuclear accumulation of β-catenin and increased TCF/Lef transcriptional activity. FzD7 was identified as a putative rece...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research