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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Inactivation of AMPK Mediates High Phosphate-Induced Extracellular Matrix Accumulation via NOX4/TGF beta-1 Signaling in Human Mesangial Cells

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Papadimitriou, Alexandros [1] ; Peixoto, Elisa B. M. I. [1] ; Silva, Kamila C. [1] ; Lopes de Faria, Jacqueline M. [1] ; Lopes de Faria, Jose B. [1]
Total Authors: 5
[1] Univ Estadual Campinas, Fac Med Sci, Renal Pathophysiol Lab Invest Diabet Complica, NMCE, BR-13083877 Campinas, SP - Brazil
Total Affiliations: 1
Document type: Journal article
Source: CELLULAR PHYSIOLOGY AND BIOCHEMISTRY; v. 34, n. 4, p. 1260-1272, 2014.
Web of Science Citations: 13

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), fibronectin (F/N), collagen IV (C-IV) and alpha-smooth muscle actin (alpha-SMA) expression was assessed via western blot and immunofluorescence. 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, alpha-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 a-SMA expression. Conclusion: AMPK inactivation with NOX4-induced ROS formation and transforming growth factor beta-1 (TGF beta-1) signaling activation mediates high Pi-induced ECM accumulation in iHMCs. Maneuvers increasing AMPK or reducing NOX4 activity may contribute to renal protection under hyperphosphatemia. Copyright (C) 2014 S. Karger AG, Basel (AU)

FAPESP's process: 12/22452-8 - Can theobromine stimulate SIRT1 (silent information regulator 1) and reduce Diabetes-associated oxidative stress and renal fibrosis?
Grantee:Jose Butori Lopes de Faria
Support type: Regular Research Grants
FAPESP's process: 08/57560-0 - Effects of green tea (Camellia sinensis), cocoa and nitric oxide donor on diabetic nephropathy and retinopathy: contribution of the reduction of oxidative stress and inflammation and elevation of nitric oxide
Grantee:Jose Butori Lopes de Faria
Support type: Research Projects - Thematic Grants