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Distinct global DNA methylation and NF-kappa B expression profile of preimplantation biopsies from ideal and non-ideal kidneys

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Goncalves, Naiane do Nascimento ; Caldas, Heloisa Cristina ; da Silva Florim, Greiciane Maria ; Sormani, Giovanna Mattiello ; Rebolho Batista Arantes, Lidia Maria ; Sorroche, Bruna Pereira ; Sperto Ferreira Baptista, Maria Alice ; Maximina Fernandes-Charpiot, Ida Maria ; Viese Nascimento-Filho, Carlos Henrique ; de Castilho, Rogerio Moraes ; Abbud-Filho, Mario
Total Authors: 11
Document type: Journal article
Source: JOURNAL OF NEPHROLOGY; v. 35, n. 7, p. 10-pg., 2022-09-01.
Abstract

Background Epigenetic mechanisms may affect the ideal and non-ideal kidneys selected for transplantation and their inflammatory gene expression profile differently and may contribute to poor clinical outcomes. Objective Study the Global DNA methylation and the expression profiles of the DNA methyltransferases (DNMTs) and nuclear factor kappa B (NF-kappa B) in preimplantation kidney biopsies from ideal and non-ideal kidneys (expanded criteria donor (ECD) and with KDPI> 85%). Methods In a sample consisting of 45 consecutive pre-implantation biopsies, global DNA methylation levels were detected by LINE-1 repeated elements using bisulfite pyrosequencing. DNMT gene expression was assessed by real-time quantitative polymerase chain reaction, and NF-kappa B protein expression by immunofluorescence. Results ECD kidneys displayed increased methylation levels in LINE-1, and DNMT1 and DNMT3B expression was upregulated when comparing ECD to standard criteria donor kidneys. Similarly, kidneys with KDPI> 85% exhibited increased LINE-1 methylation and DNMT1 upregulation when compared to a KDPI <= 85%. NF-kappa B protein expression levels were greatly increased in both types of non-ideal kidneys compared to ideal kidneys. Moreover, hypermethylation of LINE-1 was associated with cold ischemia time > 20 h and ECD kidney classification. Conclusions This study shows that global DNA hypermethylation and high expression of NF-kappa B occurred in both types of non-ideal kidneys and were associated with prolonged cold ischemia time. Global DNA methylation can be a useful tool to assess non-ideal kidneys and hence, could be used to expand the pool of kidneys donors. [GRAPHICS] . (AU)

FAPESP's process: 16/08301-8 - EVALUATION OF GLOBAL PROFILE OF DNA METHYLATION IN KIDNEY DONORS BASED ON EXPANDED CRITERIA DONORS
Grantee:Naiane Do Nascimento Gonçalves
Support Opportunities: Scholarships in Brazil - Doctorate