Knockdown of ANGPTL-4 inhibits inflammatory response and extracellular matrix accumulation in glomerular mesangial cells cultured under high glucose condition

Abstract

Diabetic nephropathy (DN) is one of the major diabetic complications that lead to end-stage renal failure. Angiopoietin-like protein-4 (ANGPTL-4) has been reported to be dysregulated in diabetes mellitus and diabetic complications. However, the role of ANGPTL-4 in glomerular mesangial cells (MCs) during DN remains unclear. In the present study, we evaluated the role of ANGPTL-4 in MCs in response to high glucose (HG) condition and the potential mechanism. The results proved that ANGPTL-4 expression is significantly increased in HG-stimulated MCs. Knockdown of ANGPTL-4 suppressed HG-induced cell proliferation of MCs. The production of pro-inflammatory cytokines including TNF-α, IL-1β, IL-6 were decreased in ANGPTL-4 knocked down MCs. Inhibition of ANGPTL-4 markedly suppressed the expressions of extracellular matrix (ECM) proteins, collagen IV (Col IV) and fibronectin (FN), in HG-stimulated MCs. Furthermore, ANGPTL-4 knockdown inhibited the HG-induced activation of NF-κB signaling pathway in MCs. Collectively, knockdown of ANGPTL-4 suppressed HG-induced cell proliferation, inflammatory response, and ECM accumulation inhibiting NF-κB signaling pathway in MCs. These findings suggested that ANGPTL-4 might be a therapeutic target for the prevention and treatment of DN.