Veloso Pereira, Beatriz Maria
da Silva, Karolline S.
Fabre, Nelly T.
Correa-Giannella, Maria Lucia
Número total de Autores: 7
Afiliação do(s) autor(es):
 Univ Sao Paulo, Inst Ciencias Biomed, Dept Fisiol & Biofis, Lab Bases Celulares & Mol Fisiol Renal, Sao Paulo, SP - Brazil
 Univ Sao Paulo, Lab Lipides LIM 10, Fac Med, Hosp Clin HCFMUSP, Sao Paulo, SP - Brazil
 Univ Sao Paulo, Lab Carboidratos & Radioimunoensaio LIM 18, Fac Med, Hosp Clin HCFMUSP, Sao Paulo, SP - Brazil
 Univ Nove Julho UNINOVE, Programa Posgrad Med, Sao Paulo, SP - Brazil
Número total de Afiliações: 4
Tipo de documento:
APR 1 2021.
Citações Web of Science:
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, Col4al, 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. (AU)