Artículos de revistas
Inactivation Of Ampk Mediates High Phosphate-induced Extracellular Matrix Accumulation Via Nox4/tgfβ-1 Signaling In Human Mesangial Cells
Registro en:
Cellular Physiology And Biochemistry. S. Karger Ag, v. 34, n. 4, p. 1260 - 1272, 2014.
10158987
10.1159/000366336
2-s2.0-84908615597
Autor
Papadimitriou A.
Peixoto E.B.M.I.
Silva K.C.
Lopes De Faria J.M.
Lopes De Faria J.B.
Institución
Resumen
Background/Aims: High phosphate (Pi) levels and extracellular matrix (ECM) accumulation are associated with chronic kidney disease progression. However, how high Pi levels contribute to ECM accumulation in mesangial cells is unknown. The present study investigated the role and mechanism of high Pi levels in ECM accumulation in immortalized human mesangial cells (iHMCs). Methods: iHMCs were exposed to normal (0.9 mM) or increasing Pi concentrations (2.5 and 5 mM) with or without diferent blockers or activators. NOX4, phosphorylated AMPK (p-AMPK), phosphorylated SMAD3 (p-SMAD3), fbronectin (F/N), collagen IV (C-IV) and alpha-smooth muscle actin (α-SMA) expression was assessed via western blot and immunofuorescence. Lucigenin-enhanced chemiluminescence, and dihydroethidium (DHE) assessed NADPH oxidase activity and superoxide (SO), respectively. Results: In iHMCs, a Pi transporter blocker (PFA) abrogated high Pi-induced AMPK inactivation, increase in NADPH oxidase-induced reactive oxygen species (ROS) levels, NOX4, p-SMAD3, α-SMA and C-IV expression. AMPK activation by AICAR, NOX4 silencing or NADPH oxidase blocker prevented high Pi-induced DHE levels, p-SMAD3, F/N, C-IV and α-SMA expression. Conclusion: AMPK inactivation with NOX4-induced ROS formation and transforming growth factor β-1 (TGFβ-1) signaling activation mediates high Pi-induced ECM accumulation in iHMCs. 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