(Pro)renin receptor promotes crescent formation via the ERK1/2 and Wnt/ β-catenin pathways in glomerulonephritis.

(Pro)renin receptor promotes crescent formation via the ERK1/2 and Wnt/β-catenin pathways in glomerulonephritis. Am J Physiol Renal Physiol. 2020 Aug 24;: Authors: Urushihara M, Kondo S, Kinoshita Y, Ozaki N, Jamba A, Nagai T, Fujioka K, Hattori T, Kagami S Abstract (Pro)renin receptor ((P)RR) has multiple functions, but its regulation and role in the pathogenesis in glomerulonephritis (GN) are poorly defined. The aims of this study were to determine the effects of direct renin inhibition (DRI) and demonstrate the role of (P)RR on the progression of crescentic GN. Anti-glomerular basement membrane (GBM) nephritis rat model developed progressive proteinuria (83.64 ± 10.49 mg/day) and glomerular crescent formation (% glomerular crescent: 62.1 ± 2.3%), accompanied by increased macrophage infiltration and glomerular expression of monocyte chemoattractant protein (MCP)-1, (P)RR, phospho-extracellular signal-regulated kinase (ERK)1/2, Wnt4 and active β-catenin. Treatment with DRI ameliorated proteinuria (20.33 ± 5.88 mg/day) and markedly reduced glomerular crescent formation (20.9 ± 2.6%), the induction of macrophage infiltration, (P)RR, phospho-ERK1/2, Wnt4 and active β-catenin. Furthermore, primary cultured parietal epithelial cells stimulated by recombinant prorenin showed significant increases in cell proliferation. Notably, while the ERK1/2 inhibitor PD98059 or (P)RR-specific siRNA treatment abolished the elevation in cell prol...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research