Reduced LRP6 expression and increase in the interaction of GSK3β with p53 contribute to podocyte apoptosis in diabetes mellitus and are prevented by green tea
| Autor: | Chiara Montemurro, P.P. Joazeiro, Kamila C. Silva, Daniel Teixeira, E. B. M. I. Peixoto, Diego Andreazzi Duarte, J. Lopes de Faria, Alexandros Papadimitriou, J. B. Lopes de Faria |
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| Rok vydání: | 2014 |
| Předmět: |
Male
medicine.medical_specialty Endocrinology Diabetes and Metabolism Biopsy Clinical Biochemistry Down-Regulation Apoptosis Biology Kidney Biochemistry End stage renal disease Podocyte Diabetes Mellitus Experimental Diabetic nephropathy Glycogen Synthase Kinase 3 Mice Microscopy Electron Transmission GSK-3 Internal medicine Rats Inbred SHR medicine In Situ Nick-End Labeling Albuminuria Animals Humans Diabetic Nephropathies Molecular Biology GSK3B Wnt Signaling Pathway Nutrition and Dietetics Glycogen Synthase Kinase 3 beta Tea Caspase 3 Podocytes LRP6 medicine.disease Rats medicine.anatomical_structure Endocrinology Low Density Lipoprotein Receptor-Related Protein-6 medicine.symptom Tumor Suppressor Protein p53 |
| Zdroj: | The Journal of nutritional biochemistry. 26(4) |
| ISSN: | 1873-4847 |
| Popis: | 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 GSK3β-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 GSK3β-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 GSK3β-p53, p53 expression, apoptosis and increased albumin influx. GSK3β blockade by BIO reduced GSK3β-p53 and podocyte apoptosis. In iMPs under HG, GT reduced apoptosis and the albumin influx by blocking GSK3β-p53 following the rise in p-LRP6 expression. These effects of GT were prevented by LRP6 siRNA or DKK-1. In conclusion, in DM, WNT inhibition, via LRP6, increases GSK3β-p53 and podocyte apoptosis. Maneuvers that inactivate GSK3β-p53, such as GT, may be renoprotective in DM. |
| Databáze: | OpenAIRE |
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