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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.)

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

Full text
Author(s):
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]
Total Authors: 9
Affiliation:
[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
Total Affiliations: 2
Document type: Journal article
Source: JOURNAL OF NUTRITIONAL BIOCHEMISTRY; v. 26, n. 4, p. 416-430, APR 2015.
Web of Science Citations: 13
Abstract

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)

FAPESP's process: 10/05841-5 - Oxidative stress contribution for glomerular filtration barrier integrity in diabetic and hipertensive rats
Grantee:Elisa Mauro Peixoto Prado
Support Opportunities: Scholarships in Brazil - Post-Doctoral
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 Opportunities: Research Projects - Thematic Grants