Reduced LRP6 expression and increase in the interaction of GSK3 beta with p53 contribute to podocyte apoptosis in diabetes mellitus and are prevented by green tea

Autor(es)

Peixoto, E. B. ^[1] ; Papadimitriou, A. ^[1] ; Teixeira, D. A. T. ^[1] ; Montemurro, C. ^[1] ; Duarte, D. A. ^[1] ; Silva, K. C. ^[1] ; Joazeiro, P. P. ^[2] ; Lopes de Faria, J. M. ^[1] ; Lopes de Faria, J. B. ^[1]

Afiliação do(s) autor(es)

^[1] State Univ Campinas Unicamp, Renal Pathophysiol Lab, Invest Diabet Complicat, Fac Med Sci, Sao Paulo - Brazil

^[2] State Univ Campinas Unicamp, Inst Biol, Dept Histol & Embryol, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF NUTRITIONAL BIOCHEMISTRY; v. 26, n. 4, p. 416-430, APR 2015.
• Citações Web of Science: 13

Resumo

In diabetes mellitus (DM), podocyte apoptosis leads to albuminuria and nephropathy progression. Low-density lipoprotein receptor-related protein 6 (LRP6) is WNT pathway receptor that is involved in podocyte death, adhesion and motility. Glycogen synthase kinase 3 (GSK3) interaction with p53 (GSK3-p53) promotes apoptosis in carcinoma cells. It is unknown if GSK3-p53 contributes to podocyte apoptosis in DM. In experimental DM, green tea (GT) reduces albuminuria by an unknown mechanism. In the present study, we assessed the role of the GSK33-p53 in podocyte apoptosis and the effects of GT on these abnormalities. In diabetic spontaneously hypertensive rats (SHRs), GT prevents podocyte's p-LRP6 expression reduction, increased GSK3p-p53 and high p53 levels. In diabetic SHR rats, GT reduces podocyte apoptosis, foot process effacement and albuminuria. In immortalized mouse podocytes (iMPs), high glucose (HG), silencing RNA (siRNA) or blocking LRP6 (DKK-1) reduced p-LRP6 expression, leading to high GSK3p-p53, p53 expression, apoptosis and increased albumin influx. GSK3 beta. blockade by BID reduced GSK3p-p53 and podocyte apoptosis. In iMPs under HG, GT reduced apoptosis and the albumin influx by blocking GSK3 beta-p53 following the rise in p-LRP6 expression. These effects of CT were prevented by LRP6 siRNA or DKK-1. In conclusion, in DM, WNT inhibition, via LRP6, increases GSK3p-p53 and podocyte apoptosis. Maneuvers that inactivate GSK33-p53, such as GT, may be renoprotective in DM. (C) 2015 Elsevier Inc. All rights reserved. (AU)

• Processo FAPESP: 10/05841-5 - Contribuição do estresse oxidativo para a integridade da barreira de filtração glomerular em ratos diabéticos e hipertensos
• Beneficiário: Elisa Mauro Peixoto Prado
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• 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