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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.)

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

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Author(s):
Thieme, Karina [1] ; Veloso Pereira, Beatriz Maria [1] ; da Silva, Karolline S. [2] ; Fabre, Nelly T. [3] ; Catanozi, Sergio [2] ; Passarelli, Marisa [4, 2] ; Correa-Giannella, Maria Lucia [4, 3]
Total Authors: 7
Affiliation:
[1] Univ Sao Paulo, Inst Ciencias Biomed, Dept Fisiol & Biofis, Lab Bases Celulares & Mol Fisiol Renal, Sao Paulo, SP - Brazil
[2] Univ Sao Paulo, Lab Lipides LIM 10, Fac Med, Hosp Clin HCFMUSP, Sao Paulo, SP - Brazil
[3] Univ Sao Paulo, Lab Carboidratos & Radioimunoensaio LIM 18, Fac Med, Hosp Clin HCFMUSP, Sao Paulo, SP - Brazil
[4] Univ Nove Julho UNINOVE, Programa Posgrad Med, Sao Paulo, SP - Brazil
Total Affiliations: 4
Document type: Journal article
Source: Life Sciences; v. 270, APR 1 2021.
Web of Science Citations: 1
Abstract

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)

FAPESP's process: 16/15603-0 - Unraveling mechanisms of glycemic control and chronic complications of Diabetes mellitus: contributions to human health
Grantee:Ubiratan Fabres Machado
Support type: Research Projects - Thematic Grants
FAPESP's process: 13/00713-7 - Effects of chronic administration of albumin modified by advanced glycation (age) on liver tissue: characterization of histological, inflammatory and antioxidant profile
Grantee:Nelly Takashima Fabre
Support type: Scholarships in Brazil - Master
FAPESP's process: 12/18724-2 - Advanced glycated albumin and insulin resistance in rats: focus on periepididimal adipose tissue and N-acetylcysteine actions
Grantee:Karolline Santana da Silva
Support type: Scholarships in Brazil - Doctorate
FAPESP's process: 14/17251-9 - The effects of chronic administration of albumin modified by advanced glycation (AGE) on renal tissue: characterization of the inflammatory, antioxidant and epigenetic profile
Grantee:Karina Thieme
Support type: Scholarships in Brazil - Post-Doctorate
FAPESP's process: 19/10583-0 - Epigenetic regulation of TET and Klotho proteins in Glomerular Disease
Grantee:Beatriz Maria Veloso Pereira
Support type: Scholarships in Brazil - Doctorate
FAPESP's process: 18/00573-4 - The role of DNA (hydroxy)methylation in podocytes dysfunction: epigenetic perspectives for the treatment of Chronic Kidney Disease
Grantee:Karina Thieme
Support type: Research Grants - Young Investigators Grants
FAPESP's process: 12/04831-1 - New players in glycemic control and chronic complications of Diabetes mellitus: preventive and therapeutic perspectives
Grantee:Ubiratan Fabres Machado
Support type: Research Projects - Thematic Grants
FAPESP's process: 16/04591-1 - Non-coding RNAs in diabetic kidney disease
Grantee:Karina Thieme
Support type: Scholarships abroad - Research Internship - Post-doctor