Liraglutide suppresses production of extracellular matrix proteins and ameliorates renal injury of diabetic nephropathy by enhancing Wnt/ β-catenin signaling.

Liraglutide suppresses production of extracellular matrix proteins and ameliorates renal injury of diabetic nephropathy by enhancing Wnt/β-catenin signaling. Am J Physiol Renal Physiol. 2020 Jul 27;: Authors: Huang L, Lin T, Shi M, Chen X, Wu P Abstract The Wnt/β-catenin signaling pathway is involved in the production of extracellular matrix (ECM) by mesangial cells (MCs). Recent studies by us and others demonstrated that glucagon-like peptide-1 receptor agonists (GLP-1RAs) have protective effects against diabetic nephropathy. The purpose of this study was to investigate whether the Wnt/β-catenin signaling in MCs contributed to GLP-1RA-induced inhibition of ECM accumulation and mitigation of glomerular injury in diabetic nephropathy. In cultured human mesangial cells (HMCs), liraglutide (a GLP-1RA) treatment significantly reduced high glucose (HG)-stimulated production of fibronectin (FN), collagen IV (Col IV) and α-smooth muscle actin (α-SMA) and the liraglutide effects were significantly attenuated by XAV-939, a selective inhibitor of the Wnt/β-catenin signaling. Furthermore, HG treatment significantly decreased the protein abundance of Wnt4, Wnt5a, phospho-glycogen synthase kinase-3β and β-catenin. These HG effects on the Wnt/β-catenin signaling proteins were significantly blunted by liraglutide treatment. For in vivo studies, we administered liraglutide (200μg/kg/12h) by subcutaneous injection to streptozocin-induced ty...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research