Endothelin-1 regulation is entangled in a complex web of epigenetic mechanisms in diabetes

Title:

Endothelin-1 regulation is entangled in a complex web of epigenetic mechanisms in diabetes

Creator:

Biswas, S., Feng, B., Chakrabarti, S., Sadikovic, B., Aref-Eshghi, E., Chen, S., and Thomas, A.

Identifier:

https://cdk.lib.cas.cz/client/handle/uuid:a7c6b844-5758-4d37-b3b9-dbf83c53389b
uuid:a7c6b844-5758-4d37-b3b9-dbf83c53389b
issn:0862-8408

Subject:

fyziologie člověka, human physiology, ET-1, Epigenetics, lncRNAs, DNA methylation, Histone methylation, 14, and 612

Type:

model:article and TEXT

Format:

print, bez média, and svazek

Description:

Endothelial cells (ECs) are primary targets of glucose-induced tissue damage. As a result of hyperglycemia, endothelin-1 (ET-1) is upregulated in organs affected by chronic diabetic complications. The objective of the present study was to identify novel transcriptional mechanisms that influence ET-1 regulation in diabetes. We carried out the investigation in microvascular ECs using multiple approaches. ECs were incubated with 5 mM glucose (NG) or 25 mM glucose (HG) and analyses for DNA methylation, histone methylation, or long non-coding RNA- mediated regulation of ET-1 mRNA were then performed. DNA methylation array analyses demonstrated the presence of hypomethylation in the proximal promoter and 5’ UTR/first exon regions of EDN1 following HG culture. Further, globally blocking DNA methylation or histone methylation significantly increased ET-1 mRNA expressions in both NG and HG-treated HRECs. While, knocking down the pathogenetic lncRNAs ANRIL, MALAT1, and ZFAS1 subsequently prevented the glucose-induced upregulation of ET-1 transcripts. Based on our past and present findings, we present a novel paradigm that reveals a complex web of epigenetic mechanisms regulating glucose-induced transcription of ET-1. Improving our understanding of such processes may lead to better targeted therapies., S. Biswas, B. Feng, A. Thomas, S. Chen, E. Aref-Eshghi, B. Sadikovic, S. Chakrabarti., and Seznam literatury

Language:

English

Rights:

http://creativecommons.org/publicdomain/mark/1.0/
policy:public

Source:

Physiological research | 2018 Volume:67 | Number:Suppl 1

Harvested from:

CDK

Metadata only:

false