High Glucose Induces Endothelial COX2 and iNOS Expression via Inhibition of Monomethyltransferase SETD8 Expression
Joint Authors
Qi, Jie
Wu, Qichao
Cheng, Qian
Chen, Xiangyuan
Zhu, Minmin
Miao, Changhong
Source
Issue
Vol. 2020, Issue 2020 (31 Dec. 2020), pp.1-10, 10 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2020-02-24
Country of Publication
Egypt
No. of Pages
10
Main Subjects
Abstract EN
Cyclooxygenase 2 (COX2) and inducible nitric oxide synthase (iNOS) overexpression results in endothelial apoptosis, thus mediating vascular endothelial injury in hyperglycaemia.
E26 transformation-specific sequence transcription factor-1 (ESE-1), which belongs to the E26 transformation-specific family of transcription factors, has been demonstrated to be involved in COX2 and iNOS gene transcription.
Our previous study indicated that SET domain-containing protein 8 (SETD8) downregulation is involved in high glucose-mediated endothelial inflammation in human umbilical vein endothelial cells (HUVECs).
Here, we report that SETD8 plays a major role in hyperglycaemia-induced COX2 and iNOS expression.
In HUVECs, upregulation of ESE-1 expression was related to high glucose-mediated apoptosis and COX2 and iNOS expression.
High glucose inhibited SETD8 expression, and overexpression of SETD8 diminished the effects of high glucose treatment.
Consistently, RNA silencing of SETD8 led to the opposite effect.
Furthermore, SETD8 was found to interact with specificity protein 1 (SP1).
Blockade of SP1 protected against high glucose-mediated endothelial injury.
Mechanistically, we showed that H4K20me1, a downstream target of SETD8, and SP1 were enriched at the ESE-1 promoter region by ChIP assay.
Luciferase reporter assays indicated that SETD8 overexpression attenuated ESE-1 promoter activity and augmented the inhibitory effect of siSP1 on ESE-1 promoter activity.
In general, our data indicate that SETD8 interacts with SP1 to coregulate ESE-1 expression, which is involved in hyperglycaemia-mediated endothelial apoptosis in HUVECs.
American Psychological Association (APA)
Qi, Jie& Wu, Qichao& Cheng, Qian& Chen, Xiangyuan& Zhu, Minmin& Miao, Changhong. 2020. High Glucose Induces Endothelial COX2 and iNOS Expression via Inhibition of Monomethyltransferase SETD8 Expression. Journal of Diabetes Research،Vol. 2020, no. 2020, pp.1-10.
https://search.emarefa.net/detail/BIM-1182938
Modern Language Association (MLA)
Qi, Jie…[et al.]. High Glucose Induces Endothelial COX2 and iNOS Expression via Inhibition of Monomethyltransferase SETD8 Expression. Journal of Diabetes Research No. 2020 (2020), pp.1-10.
https://search.emarefa.net/detail/BIM-1182938
American Medical Association (AMA)
Qi, Jie& Wu, Qichao& Cheng, Qian& Chen, Xiangyuan& Zhu, Minmin& Miao, Changhong. High Glucose Induces Endothelial COX2 and iNOS Expression via Inhibition of Monomethyltransferase SETD8 Expression. Journal of Diabetes Research. 2020. Vol. 2020, no. 2020, pp.1-10.
https://search.emarefa.net/detail/BIM-1182938
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1182938