| Texto completo | |
| Autor(es): |
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]
Número total de Autores: 5
|
| Afiliação do(s) autor(es): | [1] Univ Estadual Campinas, Fac Med Sci, Renal Pathophysiol Lab Invest Diabet Complica, NMCE, BR-13083877 Campinas, SP - Brazil
Número total de Afiliações: 1
|
| Tipo de documento: | Artigo Científico |
| Fonte: | CELLULAR PHYSIOLOGY AND BIOCHEMISTRY; v. 34, n. 4, p. 1260-1272, 2014. |
| Citações Web of Science: | 13 |
| Resumo | |
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) | |
| Processo FAPESP: | 12/22452-8 - A teobromina pode estimular SIRT1 (silent information regulator 1) e reduzir o estresse oxidativo e fibrose renal associados ao Diabetes mellitus? |
| Beneficiário: | Jose Butori Lopes de Faria |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |
| Processo FAPESP: | 08/57560-0 - Efeitos do chá verde (Camellia sinensis), do cacau e de um doador de óxido nítrico na nefropatia e retinopatia diabética: papel da redução do estresse oxidativo e da inflamação e do aumento do óxido nítrico |
| Beneficiário: | Jose Butori Lopes de Faria |
| Modalidade de apoio: | Auxílio à Pesquisa - Temático |