Chronic advanced-glycation end products treatment induces TXNIP expression and epigenetic changes in glomerular podocytes in vivo and in vitro.

Autor: Thieme K; Laboratorio de Bases Celulares e Moleculares da Fisiologia Renal, Departamento de Fisiologia e Biofisica, Instituto de Ciencias Biomedicas, Universidade de Sao Paulo, Sao Paulo, SP, Brazil., Pereira BMV; Laboratorio de Bases Celulares e Moleculares da Fisiologia Renal, Departamento de Fisiologia e Biofisica, Instituto de Ciencias Biomedicas, Universidade de Sao Paulo, Sao Paulo, SP, Brazil., da Silva KS; Laboratorio de Lipides (LIM-10) do Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brazil., Fabre NT; Laboratorio de Carboidratos e Radioimunoensaio (LIM-18) do Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brazil., Catanozi S; Laboratorio de Lipides (LIM-10) do Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brazil., Passarelli M; Laboratorio de Lipides (LIM-10) do Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brazil; Programa de Pos-Graduaçao em Medicina, Universidade Nove de Julho (UNINOVE), Sao Paulo, SP, Brazil., Correa-Giannella ML; Laboratorio de Carboidratos e Radioimunoensaio (LIM-18) do Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brazil; Programa de Pos-Graduaçao em Medicina, Universidade Nove de Julho (UNINOVE), Sao Paulo, SP, Brazil. Electronic address: maria.giannella@fm.usp.br.
Jazyk: angličtina
Zdroj: Life sciences [Life Sci] 2021 Apr 01; Vol. 270, pp. 118997. Date of Electronic Publication: 2021 Jan 13.
DOI: 10.1016/j.lfs.2020.118997
Abstrakt: Advanced glycation end products (AGEs) play an important role in oxidative stress and inflammation, processes implicated in the development and progression of kidney dysfunction. In the present study, we investigated the participation of the pro-oxidant protein thioredoxin-interacting protein (TXNIP) and of epigenetic mechanisms on kidney tissue (in vivo, in non-diabetic rats) and on terminally differentiated glomerular podocytes (in vitro) chronically exposed to AGEs. AGEs induced total kidney and glomerular TXNIP expression and decreased H3K27me3 content. Concomitant treatment with the antioxidant N-acetyl-cysteine (NAC) reversed only the increased TXNIP expression. TXNIP expression positively correlated with proteinuria and negatively correlated with H3K27me3 content. In vitro studies in podocytes showed that 72 h exposure to AGEs decreased nephrin expression and increased Txnip, Nox4, Col4a1, and epithelial-to-mesenchymal transition (EMT) markers (Acta2, Snail1, and Tgfb1). Podocytes treatment with NAC reversed Nox4, Col4a1, Acta2, and Tgfb1 increased expression but did not abrogate the reduced expression of nephrin. MiR-29a expression was downregulated by AGEs in vivo, but not in vitro. In conclusion, treatment of non-diabetic rats with AGEs induced TXNIP expression and decreased the contents of the repressive epigenetic mark H3K27me3 and of miR-29a, potentially driving injury to glomerular filtration barrier and podocytes dysfunction.
(Copyright © 2021 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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